{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "RNA as Structural Scaffold in Nuclear Organization", "entry_form": "claim", "gradeable_restatement": "Nascent and non-coding RNA acts as a pervasive, load-bearing physical scaffold that organizes interphase chromatin and props open euchromatin throughout the nucleus.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Species, cell type, cell-cycle phase, genomic compartment, RNA identity and intervention/extraction state specified before results.", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "RNA as Structural Scaffold in Nuclear Organization", "central_claim": "Nascent and non-coding RNA acts as a pervasive, load-bearing physical scaffold that organizes interphase chromatin and props open euchromatin throughout the nucleus.", "proposed_mechanism": "Nascent and non-coding RNA acts as a pervasive, load-bearing physical scaffold that organizes interphase chromatin and props open euchromatin throughout the nucleus.", "claimed_scope": "Mammalian interphase genome-wide load-bearing RNA material, distinguished from defined NEAT1 compartments, specialized repressive domains and mitosis; zebrafish and yeast experiments remain comparators.", "claimed_level": [ "maintenance" ], "is_conjunctive": true, "conjunctive_note": "Index scope-matched retained. SC2 and SC3 represent the global scope; SC1 local compartment causality cannot carry the global meshwork." }, "rubric_routing": { "primary_rubric": "03-epigenetics-gene-regulation.md", "secondary_rubrics": [], "index_notes_applied": [ "Index scope-matched retained. SC2 and SC3 represent the global scope; SC1 local compartment causality cannot carry the global meshwork." ], "rubric_fit_note": "Rubric03 fits structural nuclear phenotypes and native RNA/protein architecture. Compartment integrity and chromatin compaction are the stated structural outcomes; clinical disease is not required. The exact index separates specific architectural RNA compartments from the pan-nuclear material claim. Native intact-cell and mouse perturbation are distinguished from purified reconstitution and extracted-nucleus RNase." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Specific architectural RNAs nucleate defined nuclear compartments.", "subclaim_type": "mechanism", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Ζ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "For defined NEAT1-dependent paraspeckle assembly, RNA depletion, mouse genetic loss and endogenous RNA-domain editing/rescue provide complementary causal support across cellular and animal systems. These justify Ζ for the existential subclaim that specific RNAs nucleate defined compartments; they do not establish equivalent necessity/sufficiency for every XIST, MATR3 or LINE1 example, every RNA body, or endogenous liquid-phase physics. Those separate local mechanisms retain source-specific boundaries." }, { "id": "SC2", "statement": "A pan-nuclear nascent RNA meshwork is structurally necessary to keep bulk euchromatin decompacted.", "subclaim_type": "necessity", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "SAF-A perturbation/rescue, regional compaction and transcription/RNA-linked microphase studies provide substantial mechanistic evidence, while repeat-rich scaffold extraction and rapid physical redistribution strengthen a physical contribution. However, global protein loss, polymerase/RNA attachment, transcription termination and permeabilized RNase do not selectively isolate a necessary pan-nuclear RNA material in intact interphase cells. The global load-bearing requirement remains Γ; narrow RNA-protein architecture contributions are not denied." }, { "id": "SC3", "statement": "Local RNA scaffold mechanisms generalise to the whole interphase genome.", "subclaim_type": "generalization", "scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "claimed_scope": "Endogenous locus, cell state, temporal resolution and intervention specified before outcomes", "governing_rubric": "03-epigenetics-gene-regulation.md", "key_evidence_anchor": "Original perturbation with functional transcription/architecture and specificity controls", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Defined RNA compartments, repeat heterochromatin, specialized lncRNA domains and mitotic remodeling are causal in their contexts. They have different outputs, signs and dependencies and cannot be stitched into a single necessary bulk-euchromatin mechanism. Global RNA-chromatin contacts often follow proximity. Local-to-global inference remains Γ, with mapped boundaries preserved rather than fitted to successful responses." } ], "aggregation_rule": "scope-matched", "aggregation_preregistered": true, "aggregation_rationale": "Index scope-matched retained. SC2 and SC3 represent the global scope; SC1 local compartment causality cannot carry the global meshwork.", "primary_subclaim_id": "SC2", "aggregation_derivation": "Scope-matched aggregation gives Γ for the global meshwork (SC2/SC3). Specific RNA-dependent compartment nucleation retains Ζ under its local scope; it cannot carry the whole-interphase requirement. Strong positive RNA-protein structure studies prevent a purely associational dismissal, but no examined live global RNA-selective loss/rescue isolates necessary load-bearing material from the act of transcription or protein functions.", "aggregation_alternatives": { "weakest_link_would_return": "Γ", "primary_subclaim_would_return": "Γ", "scope_matched_would_return": "Γ", "note": "Separate narrow successes do not replace the preregistered full-scope gate." }, "index_rule_deviation": "Subclaim text narrowed relative to hypothesis-index.md: the index states SC1 as the necessity-and-sufficiency claim for NEAT1, XIST and MATR3/LINE1, whereas SC1 is scored here on the narrower existential form (specific RNAs nucleate defined compartments), because the necessity-and-sufficiency conjunction is not established for every named example. The declared aggregation rule (scope-matched) is unchanged and the headline is taken from SC2/SC3, so the narrowing does not move the overall letter." }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M3", "is_nominal": false, "name": "Specific architectural RNA compartments", "core_claim": "Defined RNA-protein assemblies organize selected compartments and domains without requiring one global matrix.", "explains_what_nominal_does_not": "Defined RNA-protein assemblies organize selected compartments and domains without requiring one global matrix.", "strongest_supporting_evidence": [ "NEAT1 depletion, domain assembly/rescue and mouse body loss provide complementary native causal tests; specialized LINE1 and Firre contexts add mechanism." ], "strongest_contradictory_evidence": [ "These studies do not prove all other nascent RNA is a passive by-product; broad RNA contributions remain plausible." ], "hsef_level_for_this_model": "Ζ", "rationale": "NEAT1 depletion, domain assembly/rescue and mouse body loss provide complementary native causal tests; specialized LINE1 and Firre contexts add mechanism. These studies do not prove all other nascent RNA is a passive by-product; broad RNA contributions remain plausible." }, { "rank_in_tournament": 2, "model_id": "M2", "is_nominal": false, "name": "Transcription and tethered microphase organization", "core_claim": "Polymerase attachment, RNA-rich phases and biochemical work organize active chromatin in specified contexts.", "explains_what_nominal_does_not": "Polymerase attachment, RNA-rich phases and biochemical work organize active chromatin in specified contexts.", "strongest_supporting_evidence": [ "Flavopiridol versus polymerase-retaining actinomycin D, RNA-rich pockets and cross-cell replication support a tether-dependent context mechanism." ], "strongest_contradictory_evidence": [ "Different drugs affect several molecular processes; a pure transcript-free moving-barrier account is not uniquely identified." ], "hsef_level_for_this_model": "Ε", "rationale": "Flavopiridol versus polymerase-retaining actinomycin D, RNA-rich pockets and cross-cell replication support a tether-dependent context mechanism. Different drugs affect several molecular processes; a pure transcript-free moving-barrier account is not uniquely identified." }, { "rank_in_tournament": 3, "model_id": "M1", "is_nominal": true, "name": "Global RNA load-bearing mesh", "core_claim": "Nascent/noncoding RNA physically props open bulk euchromatin throughout interphase.", "explains_what_nominal_does_not": "Nascent/noncoding RNA physically props open bulk euchromatin throughout interphase.", "strongest_supporting_evidence": [ "SAF-A domain rescue and gene-rich compaction, scaffold fractionation, SAR RNA sensitivity and rapid RNA-protein displacement provide a substantial physical steelman." ], "strongest_contradictory_evidence": [ "No selective intact-cell global RNA loss/rescue separates RNA material necessity from polymerase attachment, proteins and extraction." ], "hsef_level_for_this_model": "Γ", "rationale": "SAF-A domain rescue and gene-rich compaction, scaffold fractionation, SAR RNA sensitivity and rapid RNA-protein displacement provide a substantial physical steelman. No selective intact-cell global RNA loss/rescue separates RNA material necessity from polymerase attachment, proteins and extraction." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Intrinsic chromatin polymer organization", "core_claim": "Chromatin affinity and polymer behavior contribute to baseline compartmentalization without one external RNA tether.", "explains_what_nominal_does_not": "Chromatin affinity and polymer behavior contribute to baseline compartmentalization without one external RNA tether.", "strongest_supporting_evidence": [ "Compartment-specific folding, RNA-rich versus chromatin-rich segregation and preserved structure in some local perturbations motivate a polymer contribution." ], "strongest_contradictory_evidence": [ "The selected corpus does not isolate an RNA-free universal baseline or establish that RNA has no causal structural role." ], "hsef_level_for_this_model": "Γ", "rationale": "Compartment-specific folding, RNA-rich versus chromatin-rich segregation and preserved structure in some local perturbations motivate a polymer contribution. The selected corpus does not isolate an RNA-free universal baseline or establish that RNA has no causal structural role." }, { "rank_in_tournament": 5, "model_id": "M5", "is_nominal": false, "name": "Classical static protein matrix", "core_claim": "A stable insoluble fibrillar protein skeleton specifies all nuclear architecture.", "explains_what_nominal_does_not": "A stable insoluble fibrillar protein skeleton specifies all nuclear architecture.", "strongest_supporting_evidence": [ "Nuclear fractionation and scaffold protein-RNA association preserve an operational insoluble framework." ], "strongest_contradictory_evidence": [ "Extraction insolubility is not living-cell static mechanics; rapid SAF-A mobility and context-specific dependencies do not establish a universal rigid skeleton." ], "hsef_level_for_this_model": "Α", "rationale": "Nuclear fractionation and scaffold protein-RNA association preserve an operational insoluble framework. Extraction insolubility is not living-cell static mechanics; rapid SAF-A mobility and context-specific dependencies do not establish a universal rigid skeleton." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. NEAT1 mouse genetic loss (PMID21444682) and RNA-domain assembly (PMID29932899) directly address defined RNA compartments. Transcriptional microphase experiments (PMID33649325) address wider euchromatin and retain polymerase/RNA-tether confounding. The distinction is scope and intervention identity; no single study establishes an exclusive universal winner.", "study_separating_rank1_from_rank2": "NEAT1 mouse genetic loss (PMID21444682) and RNA-domain assembly (PMID29932899) directly address defined RNA compartments. Transcriptional microphase experiments (PMID33649325) address wider euchromatin and retain polymerase/RNA-tether confounding. The distinction is scope and intervention identity; no single study establishes an exclusive universal winner.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "28622508", "title": "SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.", "citation": "Nozawa RS, Boteva L, Soares DC et al. SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs. Cell. 2017.", "doi": "10.1016/j.cell.2017.05.029", "pmcid": "PMC5473940", "url": "https://pubmed.ncbi.nlm.nih.gov/28622508/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28622508/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28622508", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph20, 1:Results:paragraph21, 1:Results:paragraph22, 1:Results:paragraph82, 1:Results:paragraph98. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "native human RPE1 and engineered 293 rescue cells", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "SAF-A loss compacts gene-rich regions with wild-type but not Walker-A or RGG-deficient rescue; early bulk transcription changes are limited.", "what_it_does_not_show": "RNA-sensitive fractionation uses extracted nuclear samples; tagged rescue and selected loci do not isolate a pan-nuclear load-bearing RNA mesh.", "confounders_present": [ "RNA-sensitive fractionation uses extracted nuclear samples; tagged rescue and selected loci do not isolate a pan-nuclear load-bearing RNA mesh." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 2, "pmid": "29273625", "title": "The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes.", "citation": "Fan H, Lv P, Huo X et al. The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes. Genome research. 2018.", "doi": "10.1101/gr.224576.117", "pmcid": "PMC5793783", "url": "https://pubmed.ncbi.nlm.nih.gov/29273625/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29273625/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29273625", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 0:Results:paragraph0, 0:Results:paragraph2, 0:Results:paragraph3, 0:Results:paragraph4, 0:Results:paragraph23. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse AML12 hepatocyte and human HepG2 cell models", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "HNRNPU depletion alters global compaction, LADs, compartments and loops; resistant cDNA rescues cellular architecture with cell-cycle controls.", "what_it_does_not_show": "The depleted target is multifunctional protein, not selectively RNA material; RAD21 redistribution and transcriptional changes remain alternative mediators.", "confounders_present": [ "The depleted target is multifunctional protein, not selectively RNA material; RAD21 redistribution and transcriptional changes remain alternative mediators." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 3, "pmid": "33649325", "title": "Transcription organizes euchromatin via microphase separation.", "citation": "Hilbert L, Sato Y, Kuznetsova K et al. Transcription organizes euchromatin via microphase separation. Nature communications. 2021.", "doi": "10.1038/s41467-021-21589-3", "pmcid": "PMC7921102", "url": "https://pubmed.ncbi.nlm.nih.gov/33649325/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33649325/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID34230494" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33649325", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph5, 1:Results:paragraph6, 1:Results:paragraph7, 1:Results:paragraph14. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "zebrafish postmitotic blastomeres and mouse ESCs", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Transcription-linked RNA-rich pockets segregate from DNA; flavopiridol coarsens domains while actinomycin-D-retained complexes preserve their pattern.", "what_it_does_not_show": "Different inhibitors alter polymerase and transcript attachment together; microphase modeling does not uniquely identify a mechanical RNA mesh or force-bearing rheology.", "confounders_present": [ "Different inhibitors alter polymerase and transcript attachment together; microphase modeling does not uniquely identify a mechanical RNA mesh or force-bearing rheology." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 4, "pmid": "31924447", "title": "Directed RNase H Cleavage of Nascent Transcripts Causes Transcription Termination.", "citation": "Lai F, Damle SS, Ling KK et al. Directed RNase H Cleavage of Nascent Transcripts Causes Transcription Termination. Molecular cell. 2020.", "doi": "10.1016/j.molcel.2019.12.029", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31924447/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31924447/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31924447", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "cultured cells and mouse directed ASO cleavage", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "RNase-H ASOs cleaving nascent RNA also cause XRN2-mediated polymerase termination.", "what_it_does_not_show": "This tests a major RNA-removal confound; it neither selectively abolishes global RNA structure nor proves RNA has no architectural role.", "confounders_present": [ "This tests a major RNA-removal confound; it neither selectively abolishes global RNA structure nor proves RNA has no architectural role." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 5, "pmid": "40493679", "title": "Role of the SAF-A/HNRNPU SAP domain in X chromosome inactivation, nuclear dynamics, transcription, splicing, and cell proliferation.", "citation": "Sharp JA, Sparago E, Thomas R et al. Role of the SAF-A/HNRNPU SAP domain in X chromosome inactivation, nuclear dynamics, transcription, splicing, and cell proliferation. PLoS genetics. 2025.", "doi": "10.1371/journal.pgen.1011719", "pmcid": "PMC12176297", "url": "https://pubmed.ncbi.nlm.nih.gov/40493679/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40493679/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID39314300" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID40493679", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph11, 1:Results:paragraph12, 1:Results:paragraph13, 1:Results:paragraph20, 1:Results:paragraph23. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human female RPE1 endogenous SAF-A degron and rescue", "decisive_perturbation": true, "endogenous": false, "direction": "mixed", "what_it_shows": "Near-endogenous rescue alleles separate dynamic SAP-dependent XIST localization from global RNA expression and retained maintenance-phase Xi silencing.", "what_it_does_not_show": "Rapid FRAP disproves a stable tether interpretation, not a transient load-bearing network; XIST compartment and ordinary euchromatin are different scopes.", "confounders_present": [ "Rapid FRAP disproves a stable tether interpretation, not a transient load-bearing network; XIST compartment and ordinary euchromatin are different scopes." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 6, "pmid": "33053167", "title": "Cell division requires RNA eviction from condensing chromosomes.", "citation": "Sharp JA, Perea-Resa C, Wang W et al. Cell division requires RNA eviction from condensing chromosomes. The Journal of cell biology. 2020.", "doi": "10.1083/jcb.201910148", "pmcid": "PMC7549315", "url": "https://pubmed.ncbi.nlm.nih.gov/33053167/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33053167/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33053167", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human mitotic SAF-A phosphorylation perturbation", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Aurora-B-dependent RNA eviction from chromosomes is required for normal mitotic segregation.", "what_it_does_not_show": "Prophase/nuclear-envelope breakdown is outside registered interphase bulk-euchromatin scope; cell-cycle material remodeling is not pan-nuclear interphase necessity.", "confounders_present": [ "Prophase/nuclear-envelope breakdown is outside registered interphase bulk-euchromatin scope; cell-cycle material remodeling is not pan-nuclear interphase necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 7, "pmid": "24463464", "title": "Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre.", "citation": "Hacisuleyman E, Goff LA, Trapnell C et al. Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nature structural & molecular biology. 2014.", "doi": "10.1038/nsmb.2764", "pmcid": "PMC3950333", "url": "https://pubmed.ncbi.nlm.nih.gov/24463464/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24463464/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID24463464", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph8, 1:RESULTS:paragraph10, 1:RESULTS:paragraph15, 1:RESULTS:paragraph16, 1:RESULTS:paragraph17. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse ESC Firre locus knockout and hnRNPU knockdown", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Firre locus loss or hnRNPU reduction decreases specific cross-chromosomal colocalization and alters focal RNA localization.", "what_it_does_not_show": "Whole-locus deletion, growth changes and no RNA-only local rescue limit attribution to transcript rather than DNA/transcription; selected trans sites are not global scaffolding.", "confounders_present": [ "Whole-locus deletion, growth changes and no RNA-only local rescue limit attribution to transcript rather than DNA/transcription; selected trans sites are not global scaffolding." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 8, "pmid": "29937225", "title": "A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.", "citation": "Percharde M, Lin CJ, Yin Y et al. A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity. Cell. 2018.", "doi": "10.1016/j.cell.2018.05.043", "pmcid": "PMC6046266", "url": "https://pubmed.ncbi.nlm.nih.gov/29937225/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29937225/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29937225", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse ESC and preimplantation embryos", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "LINE1 RNA recruits nucleolin and KAP1 for Dux repression and rDNA expression in early-development contexts.", "what_it_does_not_show": "Specific regulatory recruitment and self-renewal do not show all interphase euchromatin requires an open mechanical mesh.", "confounders_present": [ "Specific regulatory recruitment and self-renewal do not show all interphase euchromatin requires an open mechanical mesh." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 9, "pmid": "31677973", "title": "The Nuclear Matrix Protein SAFB Cooperates with Major Satellite RNAs to Stabilize Heterochromatin Architecture Partially through Phase Separation.", "citation": "Huo X, Ji L, Zhang Y et al. The Nuclear Matrix Protein SAFB Cooperates with Major Satellite RNAs to Stabilize Heterochromatin Architecture Partially through Phase Separation. Molecular cell. 2020.", "doi": "10.1016/j.molcel.2019.10.001", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31677973/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31677973/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31677973", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse SAFB and major-satellite RNA heterochromatin", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "SAFB-repeat RNA interactions support heterochromatin foci and genomic compartmentalization.", "what_it_does_not_show": "SAFB differs from SAF-A; compact heterochromatin is a distinct output from universal RNA-driven decompaction; phase-specific loss/rescue needs deeper access.", "confounders_present": [ "SAFB differs from SAF-A; compact heterochromatin is a distinct output from universal RNA-driven decompaction; phase-specific loss/rescue needs deeper access." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 10, "pmid": "35947677", "title": "LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes.", "citation": "Della Valle F, Reddy P, Yamamoto M et al. LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes. Science translational medicine. 2022.", "doi": "10.1126/scitranslmed.abl6057", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35947677/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35947677/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35947677", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human progeroid fibroblasts and HGPS mouse ASOs", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "LINE1 RNA accumulation inhibits SUV39H1 activity; RNA reduction restores heterochromatin and improves restricted mouse phenotypes.", "what_it_does_not_show": "Pathological RNA abundance can erode heterochromatin; chromatin marks and progeroid context do not identify a universal physical scaffold.", "confounders_present": [ "Pathological RNA abundance can erode heterochromatin; chromatin marks and progeroid context do not identify a universal physical scaffold." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 11, "pmid": "42335169", "title": "Correlated protein-RNA associations and a requirement for HNRNPU in the long-range recruitment of Polycomb Repressive Complexes by the lncRNAs Airn and Kcnq1ot1.", "citation": "Murvin MM, Li S, Abrash EW et al. Correlated protein-RNA associations and a requirement for HNRNPU in the long-range recruitment of Polycomb Repressive Complexes by the lncRNAs Airn and Kcnq1ot1. PLoS genetics. 2026.", "doi": "10.1371/journal.pgen.1012215", "pmcid": "PMC13318007", "url": "https://pubmed.ncbi.nlm.nih.gov/42335169/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42335169/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID40791421" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID42335169", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse trophoblast stem-cell lncRNA domains", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "HNRNPU loss reduces Polycomb marks across Airn/Kcnq1ot1 domains with distinct effects while their chromatin localization and PRC1 association persist.", "what_it_does_not_show": "Protein recruitment, RNA abundance and chromatin modification differ by domain; repressive multimegabase regulation is not global open-euchromatin support.", "confounders_present": [ "Protein recruitment, RNA abundance and chromatin modification differ by domain; repressive multimegabase regulation is not global open-euchromatin support." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "19188602", "title": "MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles.", "citation": "Sasaki YT, Ideue T, Sano M et al. MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proceedings of the National Academy of Sciences of the United States of America. 2009.", "doi": "10.1073/pnas.0807899106", "pmcid": "PMC2650297", "url": "https://pubmed.ncbi.nlm.nih.gov/19188602/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19188602/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID19188602", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "native cultured mammalian paraspeckles", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Efficient MENepsilon/beta depletion disintegrates paraspeckles and prevents recovery after transcription arrest.", "what_it_does_not_show": "Long NEAT1 isoform and specific RNA-protein compartment are targeted; public body unavailable, so perturbation detail beyond original abstract remains limited.", "confounders_present": [ "Long NEAT1 isoform and specific RNA-protein compartment are targeted; public body unavailable, so perturbation detail beyond original abstract remains limited." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 13, "pmid": "29932899", "title": "Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation.", "citation": "Yamazaki T, Souquere S, Chujo T et al. Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation. Molecular cell. 2018.", "doi": "10.1016/j.molcel.2018.05.019", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29932899/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29932899/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29932899", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "native haploid-cell endogenous NEAT1 domain deletions", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Native RNA-domain deletion maps assembly functions; NONO tether rescue requires its dimerization domain.", "what_it_does_not_show": "Synthetic rescue and in-vitro aggregation do not alone prove endogenous liquid-state mechanics; public body unavailable, complete original abstract examined.", "confounders_present": [ "Synthetic rescue and in-vitro aggregation do not alone prove endogenous liquid-state mechanics; public body unavailable, complete original abstract examined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 14, "pmid": "33885174", "title": "Paraspeckles are constructed as block copolymer micelles.", "citation": "Yamazaki T, Yamamoto T, Yoshino H et al. Paraspeckles are constructed as block copolymer micelles. The EMBO journal. 2021.", "doi": "10.15252/embj.2020107270", "pmcid": "PMC8204865", "url": "https://pubmed.ncbi.nlm.nih.gov/33885174/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33885174/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33885174", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "native NEAT1 deletion and transcription-modulation experiments", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "RNA terminal-domain deletions alter paraspeckle shell organization and support an experimentally tested micelle model.", "what_it_does_not_show": "Shape-prediction agreement does not demonstrate one physics for every nuclear body; public body unavailable in this run.", "confounders_present": [ "Shape-prediction agreement does not demonstrate one physics for every nuclear body; public body unavailable in this run." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 15, "pmid": "21444682", "title": "Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice.", "citation": "Nakagawa S, Naganuma T, Shioi G et al. Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice. The Journal of cell biology. 2011.", "doi": "10.1083/jcb.201011110", "pmcid": "PMC3082198", "url": "https://pubmed.ncbi.nlm.nih.gov/21444682/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21444682/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID21444682", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 1:Results and discussion:paragraph5, 1:Results and discussion:paragraph9, 1:Results and discussion:paragraph11, 1:Results and discussion:paragraph12, 1:Results and discussion:paragraph16. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "mouse Neat1 targeted allele, tissue and MEFs", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Neat1 loss, including the architectural long isoform, removes paraspeckles in cultured cells and specific adult tissues while baseline viability and examined tissue organization persist.", "what_it_does_not_show": "Compartment assembly necessity is real, but ordinary-laboratory absence of gross phenotype does not rule out stress or reproductive functions.", "confounders_present": [ "Compartment assembly necessity is real, but ordinary-laboratory absence of gross phenotype does not rule out stress or reproductive functions." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 16, "pmid": "26283796", "title": "Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles.", "citation": "Hennig S, Kong G, Mannen T et al. Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. The Journal of cell biology. 2015.", "doi": "10.1083/jcb.201504117", "pmcid": "PMC4539981", "url": "https://pubmed.ncbi.nlm.nih.gov/26283796/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26283796/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26283796", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "native paraspeckle protein depletion with domain rescue", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "RBM14 and FUS low-complexity domains are required for rescue of paraspeckle formation.", "what_it_does_not_show": "Protein domain necessity identifies cooperating scaffold chemistry, not solely RNA mechanics or a pan-nuclear matrix.", "confounders_present": [ "Protein domain necessity identifies cooperating scaffold chemistry, not solely RNA mechanics or a pan-nuclear matrix." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "11790299", "title": "Paraspeckles: a novel nuclear domain.", "citation": "Fox AH, Lam YW, Leung AK et al. Paraspeckles: a novel nuclear domain. Current biology : CB. 2002.", "doi": "10.1016/s0960-9822(01)00632-7", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11790299/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/11790299/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID11790299", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human primary and transformed cell nuclear-body imaging", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A defined paraspeckle compartment contains dynamic RNA-binding proteins and reorganizes during transcription inhibition.", "what_it_does_not_show": "Protein localization and dynamics establish the body but not RNA-specific necessity or global chromatin mechanics.", "confounders_present": [ "Protein localization and dynamics establish the body but not RNA-specific necessity or global chromatin mechanics." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "20211624", "title": "Identification of protein interaction regions of VINC/NEAT1/Men epsilon RNA.", "citation": "Murthy UM, Rangarajan PN. Identification of protein interaction regions of VINC/NEAT1/Men epsilon RNA. FEBS letters. 2010.", "doi": "10.1016/j.febslet.2010.03.003", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/20211624/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20211624/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID20211624", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse NEAT1 RNA binding-site analysis", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Distinct NEAT1 RNA regions interact with p54nrb.", "what_it_does_not_show": "Binding-site identification alone does not prove compartment assembly necessity or sufficient endogenous architecture.", "confounders_present": [ "Binding-site identification alone does not prove compartment assembly necessity or sufficient endogenous architecture." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "16148043", "title": "P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner.", "citation": "Fox AH, Bond CS, Lamond AI. P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner. Molecular biology of the cell. 2005.", "doi": "10.1091/mbc.e05-06-0587", "pmcid": "PMC1266428", "url": "https://pubmed.ncbi.nlm.nih.gov/16148043/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16148043/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID16148043", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "native paraspeckle protein interaction and transcription recovery", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "PSP1 dimer interaction and RNA-binding domain contribute to localization; bodies return when transcription resumes.", "what_it_does_not_show": "Transcription reactivation changes RNA and machinery together; protein-targeting controls do not identify global RNA load bearing.", "confounders_present": [ "Transcription reactivation changes RNA and machinery together; protein-targeting controls do not identify global RNA load bearing." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 20, "pmid": "22416126", "title": "Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation.", "citation": "Passon DM, Lee M, Rackham O et al. Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proceedings of the National Academy of Sciences of the United States of America. 2012.", "doi": "10.1073/pnas.1120792109", "pmcid": "PMC3324020", "url": "https://pubmed.ncbi.nlm.nih.gov/22416126/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22416126/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID22416126", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "DBHS structural biochemistry and cellular mutants", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "NONO/PSPC1 dimer structure and coiled-coil mutants support higher-order paraspeckle organization.", "what_it_does_not_show": "Crystal structure and mutant targeting remain local protein assembly evidence, not in-situ RNA network mechanics.", "confounders_present": [ "Crystal structure and mutant targeting remain local protein assembly evidence, not in-situ RNA network mechanics." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 21, "pmid": "29394378", "title": "Structural analyses of NEAT1 lncRNAs suggest long-range RNA interactions that may contribute to paraspeckle architecture.", "citation": "Lin Y, Schmidt BF, Bruchez MP et al. Structural analyses of NEAT1 lncRNAs suggest long-range RNA interactions that may contribute to paraspeckle architecture. Nucleic acids research. 2018.", "doi": "10.1093/nar/gky046", "pmcid": "PMC5909464", "url": "https://pubmed.ncbi.nlm.nih.gov/29394378/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29394378/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29394378", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "NEAT1 SHAPE, modeling and in-vitro RNA interaction", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "NEAT1 sequence folding and RNA-RNA interactions offer potential scaffold architecture.", "what_it_does_not_show": "Predicted or in-vitro structure is not a direct endogenous force-bearing or assembly perturbation.", "confounders_present": [ "Predicted or in-vitro structure is not a direct endogenous force-bearing or assembly perturbation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 22, "pmid": "30550788", "title": "CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development.", "citation": "Hupalowska A, Jedrusik A, Zhu M et al. CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development. Cell. 2018.", "doi": "10.1016/j.cell.2018.11.027", "pmcid": "PMC6292842", "url": "https://pubmed.ncbi.nlm.nih.gov/30550788/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30550788/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30550788", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse preimplantation embryo RNA/protein depletion", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Neat1 and p54nrb support CARM1 localization, methylation and early embryonic progression.", "what_it_does_not_show": "Transient embryo depletion and reciprocal factor effects are context specific, not proof of a universal adult interphase mesh.", "confounders_present": [ "Transient embryo depletion and reciprocal factor effects are context specific, not proof of a universal adult interphase mesh." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 23, "pmid": "27665741", "title": "Paraspeckles modulate the intranuclear distribution of paraspeckle-associated Ctn RNA.", "citation": "Anantharaman A, Jadaliha M, Tripathi V et al. Paraspeckles modulate the intranuclear distribution of paraspeckle-associated Ctn RNA. Scientific reports. 2016.", "doi": "10.1038/srep34043", "pmcid": "PMC5036046", "url": "https://pubmed.ncbi.nlm.nih.gov/27665741/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27665741/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID27665741", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mammalian Ctn RNA distribution with Neat1 loss", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Ctn RNA remains nuclear-retained without intact paraspeckles but redistributes into residual and perinucleolar foci.", "what_it_does_not_show": "Paraspeckles influence local partitioning, while nuclear retention persists through other mechanisms.", "confounders_present": [ "Paraspeckles influence local partitioning, while nuclear retention persists through other mechanisms." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 24, "pmid": "25359727", "title": "The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice.", "citation": "Nakagawa S, Shimada M, Yanaka K et al. The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development (Cambridge, England). 2014.", "doi": "10.1242/dev.110544", "pmcid": "PMC4302932", "url": "https://pubmed.ncbi.nlm.nih.gov/25359727/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25359727/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25359727", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse Neat1 knockout reproductive physiology", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Some knockout females fail corpus-luteum formation; ovarian transplant or progesterone partially rescues fertility.", "what_it_does_not_show": "The enabling suboptimal condition is unmeasured; a responder-defined scope is not acceptable, and endocrine rescue does not isolate physical scaffolding.", "confounders_present": [ "The enabling suboptimal condition is unmeasured; a responder-defined scope is not acceptable, and endocrine rescue does not isolate physical scaffolding." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 25, "pmid": "25155612", "title": "The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites.", "citation": "West JA, Davis CP, Sunwoo H et al. The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. Molecular cell. 2014.", "doi": "10.1016/j.molcel.2014.07.012", "pmcid": "PMC4428586", "url": "https://pubmed.ncbi.nlm.nih.gov/25155612/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25155612/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25155612", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human NEAT1/MALAT1 endogenous chromatin maps", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Two abundant lncRNAs occupy many active sites with distinct patterns responsive to transcription.", "what_it_does_not_show": "Widespread occupancy responds to activity and is not proof that RNA structurally supports all occupied DNA.", "confounders_present": [ "Widespread occupancy responds to activity and is not proof that RNA structurally supports all occupied DNA." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 26, "pmid": "31251911", "title": "Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription.", "citation": "Xiao R, Chen JY, Liang Z et al. Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription. Cell. 2019.", "doi": "10.1016/j.cell.2019.06.001", "pmcid": "PMC6760001", "url": "https://pubmed.ncbi.nlm.nih.gov/31251911/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31251911/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31251911", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human RBP chromatin maps and RBM25 perturbation", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "RNA-binding proteins enrich at promoters; RBM25 loss affects YY1 binding, looping and transcription.", "what_it_does_not_show": "Multifunctional protein dependence and hotspots do not identify a mechanical pan-nuclear RNA network.", "confounders_present": [ "Multifunctional protein dependence and hotspots do not identify a mechanical pan-nuclear RNA network." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 27, "pmid": "28922346", "title": "GRID-seq reveals the global RNA-chromatin interactome.", "citation": "Li X, Zhou B, Chen L et al. GRID-seq reveals the global RNA-chromatin interactome. Nature biotechnology. 2017.", "doi": "10.1038/nbt.3968", "pmcid": "PMC5953555", "url": "https://pubmed.ncbi.nlm.nih.gov/28922346/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28922346/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28922346", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human mouse Drosophila GRID-seq original maps", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Global RNA-chromatin contacts concentrate at active promoters and enhancers.", "what_it_does_not_show": "Proximity ligation and nascent transcription create contact signal; map connectivity is not RNA material necessity.", "confounders_present": [ "Proximity ligation and nascent transcription create contact signal; map connectivity is not RNA material necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 28, "pmid": "32094342", "title": "RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions.", "citation": "Bonetti A, Agostini F, Suzuki AM et al. RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions. Nature communications. 2020.", "doi": "10.1038/s41467-020-14337-6", "pmcid": "PMC7039879", "url": "https://pubmed.ncbi.nlm.nih.gov/32094342/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32094342/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID34011993" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32094342", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "mammalian RADICL-seq original maps", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Genome-wide RNA-contact mapping identifies cell-state-specific patterns with reduced nascent-transcription bias.", "what_it_does_not_show": "Intact-nuclear proximity ligation does not determine load bearing; linked correction details are unexamined.", "confounders_present": [ "Intact-nuclear proximity ligation does not determine load bearing; linked correction details are unexamined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 29, "pmid": "28132817", "title": "Systematic Mapping of RNA-Chromatin Interactions In Vivo.", "citation": "Sridhar B, Rivas-Astroza M, Nguyen TC et al. Systematic Mapping of RNA-Chromatin Interactions In Vivo. Current biology : CB. 2017.", "doi": "10.1016/j.cub.2017.01.011", "pmcid": "PMC5319903", "url": "https://pubmed.ncbi.nlm.nih.gov/28132817/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28132817/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID28222283" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28132817", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human ESC and HEK original MARGI maps", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "RNA-DNA ligation maps widespread endogenous transcript associations and distal contacts.", "what_it_does_not_show": "Cross-species control narrows ligation errors but cannot establish mechanical necessity; linked erratum remains attached.", "confounders_present": [ "Cross-species control narrows ligation errors but cannot establish mechanical necessity; linked erratum remains attached." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 30, "pmid": "37770513", "title": "Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions.", "citation": "Limouse C, Smith OK, Jukam D et al. Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions. Nature communications. 2023.", "doi": "10.1038/s41467-023-41848-9", "pmcid": "PMC10539311", "url": "https://pubmed.ncbi.nlm.nih.gov/37770513/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37770513/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID37770513", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human ESC differentiation RNA-contact maps", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Most ncRNA contacts follow three-dimensional proximity, and expression changes are unlikely explained by one ncRNA.", "what_it_does_not_show": "This opposes treating every proximity edge as specific RNA-guided control; it does not exclude collective or local scaffold effects.", "confounders_present": [ "This opposes treating every proximity edge as specific RNA-guided control; it does not exclude collective or local scaffold effects." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "21963238", "title": "Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions.", "citation": "Chu C, Qu K, Zhong FL et al. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Molecular cell. 2011.", "doi": "10.1016/j.molcel.2011.08.027", "pmcid": "PMC3249421", "url": "https://pubmed.ncbi.nlm.nih.gov/21963238/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21963238/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID21963238", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "original roX2/TERC/HOTAIR ChIRP maps", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Endogenous RNAs show focal occupancy and distinct regulatory targeting patterns.", "what_it_does_not_show": "Three specialized RNAs and mapping assays do not license a uniform genome-wide mesh; local gene regulation is not material mechanics.", "confounders_present": [ "Three specialized RNAs and mapping assays do not license a uniform genome-wide mesh; local gene regulation is not material mechanics." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 32, "pmid": "25831520", "title": "SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies.", "citation": "Kawaguchi T, Tanigawa A, Naganuma T et al. SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies. Proceedings of the National Academy of Sciences of the United States of America. 2015.", "doi": "10.1073/pnas.1423819112", "pmcid": "PMC4394320", "url": "https://pubmed.ncbi.nlm.nih.gov/25831520/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25831520/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25831520", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Strong", "system": "native mammalian SWI/SNF protein perturbations", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "SWI/SNF component loss disrupts NEAT1 and satellite-III bodies while BRG1 ATPase mutation retains paraspeckle integrity.", "what_it_does_not_show": "Noncanonical protein assembly supports RNA-dependent local bodies; complete abstract access only, no native ATPase-body paragraph audit.", "confounders_present": [ "Noncanonical protein assembly supports RNA-dependent local bodies; complete abstract access only, no native ATPase-body paragraph audit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 33, "pmid": "36354291", "title": "Paraspeckles interact with SWI/SNF subunit ARID1B to regulate transcription and splicing.", "citation": "Reddy D, Bhattacharya S, Levy M et al. Paraspeckles interact with SWI/SNF subunit ARID1B to regulate transcription and splicing. EMBO reports. 2023.", "doi": "10.15252/embr.202255345", "pmcid": "PMC9827562", "url": "https://pubmed.ncbi.nlm.nih.gov/36354291/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36354291/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID36354291", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "paraspeckle-ARID1B interactions and depletion", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "NEAT1-ARID1B interactions connect paraspeckles with transcription and splicing regulation.", "what_it_does_not_show": "Shared target expression and protein interactions are not pan-nuclear physical scaffold or phase-state-specific necessity.", "confounders_present": [ "Shared target expression and protein interactions are not pan-nuclear physical scaffold or phase-state-specific necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 34, "pmid": "35675764", "title": "A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency.", "citation": "Huang X, Bashkenova N, Hong Y et al. A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency. Cell reports. 2022.", "doi": "10.1016/j.celrep.2022.110928", "pmcid": "PMC9214724", "url": "https://pubmed.ncbi.nlm.nih.gov/35675764/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35675764/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35675764", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse stem-state TET1/PSPC1/Neat1 axis", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Neat1 modulates PRC2 binding between transcripts and bivalent promoters during cell-state transition.", "what_it_does_not_show": "Selective regulatory redistribution is different from universally propping open bulk euchromatin.", "confounders_present": [ "Selective regulatory redistribution is different from universally propping open bulk euchromatin." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 35, "pmid": "31636118", "title": "Stress granules regulate stress-induced paraspeckle assembly.", "citation": "An H, Tan JT, Shelkovnikova TA. Stress granules regulate stress-induced paraspeckle assembly. The Journal of cell biology. 2019.", "doi": "10.1083/jcb.201904098", "pmcid": "PMC6891081", "url": "https://pubmed.ncbi.nlm.nih.gov/31636118/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31636118/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31636118", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin. eLife. 2017.", "doi": "10.7554/eLife.25299", "pmcid": "PMC5538822", "url": "https://pubmed.ncbi.nlm.nih.gov/28760200/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28760200/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28760200", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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The structure of NoRC-associated RNA is crucial for targeting the chromatin remodelling complex NoRC to the nucleolus. EMBO reports. 2008.", "doi": "10.1038/embor.2008.109", "pmcid": "PMC2515205", "url": "https://pubmed.ncbi.nlm.nih.gov/18600236/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18600236/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID18600236", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing. Nature cell biology. 2009.", "doi": "10.1038/ncb1914", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19578370/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19578370/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID19578370", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. Development (Cambridge, England). 2015.", "doi": "10.1242/dev.126318", "pmcid": "PMC4529037", "url": "https://pubmed.ncbi.nlm.nih.gov/26138476/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26138476/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26138476", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases. eLife. 2017.", "doi": "10.7554/eLife.25637", "pmcid": "PMC5457138", "url": "https://pubmed.ncbi.nlm.nih.gov/28537551/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28537551/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28537551", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nature genetics. 2018.", "doi": "10.1038/s41588-018-0060-9", "pmcid": "PMC5862756", "url": "https://pubmed.ncbi.nlm.nih.gov/29483655/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29483655/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29483655", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodeling. Cell reports. 2022.", "doi": "10.1016/j.celrep.2022.110895", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35649367/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35649367/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35649367", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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Active retrotransposons help maintain pericentromeric heterochromatin required for faithful cell division. Genome research. 2020.", "doi": "10.1101/gr.256131.119", "pmcid": "PMC7605247", "url": "https://pubmed.ncbi.nlm.nih.gov/33060173/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33060173/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33060173", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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Nucleic-acid-binding properties of hnRNP-U/SAF-A, a nuclear-matrix protein which binds DNA and RNA in vivo and in vitro. European journal of biochemistry. 1994.", "doi": "10.1111/j.1432-1033.1994.tb18788.x", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8174554/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8174554/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID8174554", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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SAF-A/hnRNP-U localization in interphase and metaphase. Cytogenetic and genome research. 2009.", "doi": "10.1159/000218133", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19556781/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19556781/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID19556781", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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SAF-A forms a complex with BRG1 and both components are required for RNA polymerase II mediated transcription. PloS one. 2011.", "doi": "10.1371/journal.pone.0028049", "pmcid": "PMC3232189", "url": "https://pubmed.ncbi.nlm.nih.gov/22162999/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22162999/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID22162999", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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SAF-A has a role in transcriptional regulation of Oct4 in ES cells through promoter binding. Cellular reprogramming. 2011.", "doi": "10.1089/cell.2010.0075", "pmcid": "PMC3030915", "url": "https://pubmed.ncbi.nlm.nih.gov/21235343/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21235343/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID21235343", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. 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DNA damage triggers SAF-A and RNA biogenesis factors exclusion from chromatin coupled to R-loops removal. Nucleic acids research. 2014.", "doi": "10.1093/nar/gku601", "pmcid": "PMC4132723", "url": "https://pubmed.ncbi.nlm.nih.gov/25030905/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25030905/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25030905", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human laser damage and SAF-A/R-loop dynamics", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Damage triggers recruitment then exclusion of RNA-biogenesis factors from transcribed chromatin.", "what_it_does_not_show": "DNA damage and R-loop resolution can change scaffold localization without testing ordinary interphase architecture.", "confounders_present": [ "DNA damage and R-loop resolution can change scaffold localization without testing ordinary interphase architecture." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 50, "pmid": "34888666", "title": "SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication.", "citation": "Connolly C, Takahashi S, Miura H et al. SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication. Journal of cell science. 2022.", "doi": "10.1242/jcs.258991", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34888666/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34888666/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34888666", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "SAF-A depletion and single-cell replication analysis", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Protein loss alters licensing, fork progression and timing while damage/quiescence increase.", "what_it_does_not_show": "Replication stress and cell-state changes are major alternative causes of later chromatin phenotypes.", "confounders_present": [ "Replication stress and cell-state changes are major alternative causes of later chromatin phenotypes." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 51, "pmid": "19477957", "title": "HnRNP U mediates the long-range regulation of Shh expression during limb development.", "citation": "Zhao J, Ding J, Li Y et al. HnRNP U mediates the long-range regulation of Shh expression during limb development. Human molecular genetics. 2009.", "doi": "10.1093/hmg/ddp250", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19477957/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19477957/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID19477957", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse limb Shh mutant enhancer model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Mutant cis sequence changes hnRNPU affinity and long-range Shh regulation.", "what_it_does_not_show": "RNA-specific scaffold contribution is not isolated; inferred matrix relocation at one mutant locus cannot generalize globally.", "confounders_present": [ "RNA-specific scaffold contribution is not isolated; inferred matrix relocation at one mutant locus cannot generalize globally." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 52, "pmid": "31469911", "title": "hnRNPU/TrkB Defines a Chromatin Accessibility Checkpoint for Liver Injury and Nonalcoholic Steatohepatitis Pathogenesis.", "citation": "Xiong J, Liu T, Mi L et al. hnRNPU/TrkB Defines a Chromatin Accessibility Checkpoint for Liver Injury and Nonalcoholic Steatohepatitis Pathogenesis. Hepatology (Baltimore, Md.). 2020.", "doi": "10.1002/hep.30921", "pmcid": "PMC7048669", "url": "https://pubmed.ncbi.nlm.nih.gov/31469911/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31469911/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31469911", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse hepatocyte Hnrnpu conditional loss and injury", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Protein loss disrupts accessibility and sensitizes liver to injury through truncated TrkB signaling.", "what_it_does_not_show": "Protein, splicing/signaling and disease stress can explain effects; model does not directly remove structural RNA.", "confounders_present": [ "Protein, splicing/signaling and disease stress can explain effects; model does not directly remove structural RNA." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 53, "pmid": "40219970", "title": "Chromatin-associated α-satellite RNA maintains chromosome stability by reestablishing SAF-A in the mitotic cell cycle.", "citation": "Ren B, Zhong Y, Yang Y et al. Chromatin-associated α-satellite RNA maintains chromosome stability by reestablishing SAF-A in the mitotic cell cycle. Nucleic acids research. 2025.", "doi": "10.1093/nar/gkaf294", "pmcid": "PMC11992673", "url": "https://pubmed.ncbi.nlm.nih.gov/40219970/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40219970/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID40219970", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human centromeric RNA and SAF-A depletion in cell cycle", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Alpha-satellite RNAs support SAF-A return after mitosis, lamina reassembly and accurate segregation.", "what_it_does_not_show": "Mitotic exit and centromeric RNA are specialized contexts, not continuous necessity throughout all interphase chromatin.", "confounders_present": [ "Mitotic exit and centromeric RNA are specialized contexts, not continuous necessity throughout all interphase chromatin." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 54, "pmid": "35954396", "title": "CDC20-Mediated hnRNPU Ubiquitination Regulates Chromatin Condensation and Anti-Cancer Drug Response.", "citation": "Wavelet-Vermuse C, Odnokoz O, Xue Y et al. CDC20-Mediated hnRNPU Ubiquitination Regulates Chromatin Condensation and Anti-Cancer Drug Response. Cancers. 2022.", "doi": "10.3390/cancers14153732", "pmcid": "PMC9367339", "url": "https://pubmed.ncbi.nlm.nih.gov/35954396/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35954396/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35954396", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "breast cell CDC20-hnRNPU perturbations", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Ubiquitinated hnRNPU associates with CTCF/cohesin and alters measured condensation.", "what_it_does_not_show": "Cell-cycle regulator and protein-interaction changes do not isolate RNA material or rule out cell-state redistribution.", "confounders_present": [ "Cell-cycle regulator and protein-interaction changes do not isolate RNA material or rule out cell-state redistribution." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 55, "pmid": "40913772", "title": "Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1.", "citation": "Hsu CI, Mei S, Demmerle J et al. Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1. Cell reports. 2025.", "doi": "10.1016/j.celrep.2025.116247", "pmcid": "PMC12539602", "url": "https://pubmed.ncbi.nlm.nih.gov/40913772/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40913772/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID40913772", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse ESC NSD1 mutants and NONO depletion", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "NONO protein allosterically activates NSD1 and contributes to differentiation.", "what_it_does_not_show": "Paraspeckle-protein dependence can be protein-protein catalysis; RNA scaffold or body necessity was not isolated.", "confounders_present": [ "Paraspeckle-protein dependence can be protein-protein catalysis; RNA scaffold or body necessity was not isolated." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "42425084", "title": "RNA-dependent SFPQ condensates coordinate multidimensional regulation of extra-long neuronal genes.", "citation": "Hosokawa M, Kawakami R, Imami K et al. RNA-dependent SFPQ condensates coordinate multidimensional regulation of extra-long neuronal genes. Cell chemical biology. 2026.", "doi": "10.1016/j.chembiol.2026.06.004", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42425084/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42425084/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID42425084", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mammalian neuronal SFPQ functional perturbations", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "RNA-dependent SFPQ assemblies support extra-long gene expression and splicing.", "what_it_does_not_show": "Defined long-gene complexes and multifunctional protein perturbation are not evidence of a pervasive interphase mesh.", "confounders_present": [ "Defined long-gene complexes and multifunctional protein perturbation are not evidence of a pervasive interphase mesh." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 57, "pmid": "41105511", "title": "Long noncoding RNA-dependent control of Myc transcriptional bursting.", "citation": "Li Q, Dilsavor C, Gahramanov V et al. Long noncoding RNA-dependent control of Myc transcriptional bursting. Cell reports. 2025.", "doi": "10.1016/j.celrep.2025.116439", "pmcid": "PMC12606467", "url": "https://pubmed.ncbi.nlm.nih.gov/41105511/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41105511/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID41105511", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "native Myc/Pvt1 RNA visualizations and termination alleles", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Local Pvt1 RNA level shortens Myc burst duration; premature termination increases output and tumor phenotypes.", "what_it_does_not_show": "Termination changes the act of transcription and RNA abundance; local feedback does not show genome-wide mechanical decompaction.", "confounders_present": [ "Termination changes the act of transcription and RNA abundance; local feedback does not show genome-wide mechanical decompaction." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 58, "pmid": "41296854", "title": "CTCF-RNA interactions orchestrate cell-specific chromatin loop organization.", "citation": "Lucero K, Han S, Huang PY et al. CTCF-RNA interactions orchestrate cell-specific chromatin loop organization. Science advances. 2025.", "doi": "10.1126/sciadv.ady5507", "pmcid": "PMC12652319", "url": "https://pubmed.ncbi.nlm.nih.gov/41296854/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41296854/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID40166279" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID41296854", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "mouse ESC-neural transition CTCF RNA-region mutant and local transcript truncations", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "CTCF ZF1 and selected RNAs contribute to cell-specific loops and gene regulation.", "what_it_does_not_show": "Protein domain and transcript-truncation effects require chemistry/transcription controls; loop specificity does not establish pan-nuclear scaffolding.", "confounders_present": [ "Protein domain and transcript-truncation effects require chemistry/transcription controls; loop specificity does not establish pan-nuclear scaffolding." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 59, "pmid": "41309576", "title": "Smart 3D super-resolution microscopy reveals the architecture of the RNA scaffold in a nuclear body.", "citation": "Berrevoets ES, Kessler LF, Balakrishnan A et al. Smart 3D super-resolution microscopy reveals the architecture of the RNA scaffold in a nuclear body. Nature communications. 2025.", "doi": "10.1038/s41467-025-65723-x", "pmcid": "PMC12660752", "url": "https://pubmed.ncbi.nlm.nih.gov/41309576/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41309576/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID41309576", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "original NEAT1 3D-STED structural imaging", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Multiposition RNA labeling resolves heterogeneous paraspeckle organization and surface RNA configurations.", "what_it_does_not_show": "Particle averaging and morphology identify local structure, not a causal whole-nucleus load-bearing requirement.", "confounders_present": [ "Particle averaging and morphology identify local structure, not a causal whole-nucleus load-bearing requirement." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 60, "pmid": "34320406", "title": "Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.", "citation": "Creamer KM, Kolpa HJ, Lawrence JB. Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction. Molecular cell. 2021.", "doi": "10.1016/j.molcel.2021.07.004", "pmcid": "PMC8419111", "url": "https://pubmed.ncbi.nlm.nih.gov/34320406/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34320406/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34320406", "access_depth": "full_text_partial", "access_note": "Complete original abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph0, 1:RESULTS:paragraph3, 1:RESULTS:paragraph4, 1:RESULTS:paragraph10, 1:RESULTS:paragraph22, 1:RESULTS:paragraph27, 1:RESULTS:paragraph28, 1:RESULTS:paragraph29, 1:RESULTS:paragraph33. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human chromosome territories, fractionation and mechanical perturbation", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Repeat-rich nascent RNA persists in extracted scaffold; rapid centrifugation redistributes RNA/proteins with compaction, and RNase ablates scaffold attachment enrichment.", "what_it_does_not_show": "Strong physical support, but centrifugation redistributes several materials and RNase tests permeabilized/extracted nuclei; selective live RNA load-bearing necessity remains unresolved.", "confounders_present": [ "Strong physical support, but centrifugation redistributes several materials and RNase tests permeabilized/extracted nuclei; selective live RNA load-bearing necessity remains unresolved." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 64, "verified": 64, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC2", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Mechanistic plausibility plus in vitro reconstitution or simplified cellular support caps at Γ.", "specific_trigger": "SAF-A perturbation/rescue, regional compaction and transcription/RNA-linked microphase studies provide substantial mechanistic evidence, while repeat-rich scaffold extraction and rapid physical redistribution strengthen a physical contribution. However, global protein loss, polymerase/RNA attachment, transcription termination and permeabilized RNase do not selectively isolate a necessary pan-nuclear RNA material in intact interphase cells. The global load-bearing requirement remains Γ; narrow RNA-protein architecture contributions are not denied.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Mechanistic plausibility plus in vitro reconstitution or simplified cellular support caps at Γ.", "specific_trigger": "Defined RNA compartments, repeat heterochromatin, specialized lncRNA domains and mitotic remodeling are causal in their contexts. They have different outputs, signs and dependencies and cannot be stitched into a single necessary bulk-euchromatin mechanism. Global RNA-chromatin contacts often follow proximity. Local-to-global inference remains Γ, with mapped boundaries preserved rather than fitted to successful responses.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Nascent and non-coding RNA acts as a pervasive, load-bearing physical scaffold that organizes interphase chromatin and props open euchromatin throughout the nucleus.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "The local RNA-body subclaim assembles endogenous RNA depletion, genetic loss, domain tests and animal body absence; purified droplets or synthetic rescue are not allowed to carry it alone. They complement different errors, so the set is not re-capped as in-vitro-only. For SC2/SC3, global protein depletion, extracted-nucleus digestion and broad transcription inhibitors retain their inference limits; local causal bodies do not transfer necessity to bulk euchromatin.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Endogenous degron of a condensate component with matched rescue, AND evidence that the specific condensate state (not generic protein loss) drives the phenotype\n- Locus-specific disruption of looping with locus-specific effect\n- Combinatorial histone-mark perturbation showing direct output dependence\n- Critically: specificity against cell-cycle collapse, global transcriptional collapse, and replication stress must be demonstrated", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID19188602, PMID29932899, PMID21444682", "gamma_hard_rules_triggered": [ "Widespread RNA contact, insolubility or body presence does not alone establish mechanical load-bearing necessity.", "Native RNA/protein functional perturbations are positive within their precise contexts; the broad necessity test must separate transcript material from polymerase attachment, splicing, protein recruitment, replication stress and extraction." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "For defined NEAT1-dependent paraspeckle assembly, RNA depletion, mouse genetic loss and endogenous RNA-domain editing/rescue provide complementary causal support across cellular and animal systems. These justify Ζ for the existential subclaim that specific RNAs nucleate defined compartments; they do not establish equivalent necessity/sufficiency for every XIST, MATR3 or LINE1 example, every RNA body, or endogenous liquid-phase physics. Those separate local mechanisms retain source-specific boundaries.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Endogenous degron of a condensate component with matched rescue, AND evidence that the specific condensate state (not generic protein loss) drives the phenotype\n- Locus-specific disruption of looping with locus-specific effect\n- Combinatorial histone-mark perturbation showing direct output dependence\n- Critically: specificity against cell-cycle collapse, global transcriptional collapse, and replication stress must be demonstrated", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Widespread RNA contact, insolubility or body presence does not alone establish mechanical load-bearing necessity.", "Native RNA/protein functional perturbations are positive within their precise contexts; the broad necessity test must separate transcript material from polymerase attachment, splicing, protein recruitment, replication stress and extraction." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "SAF-A perturbation/rescue, regional compaction and transcription/RNA-linked microphase studies provide substantial mechanistic evidence, while repeat-rich scaffold extraction and rapid physical redistribution strengthen a physical contribution. However, global protein loss, polymerase/RNA attachment, transcription termination and permeabilized RNase do not selectively isolate a necessary pan-nuclear RNA material in intact interphase cells. The global load-bearing requirement remains Γ; narrow RNA-protein architecture contributions are not denied.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Endogenous degron of a condensate component with matched rescue, AND evidence that the specific condensate state (not generic protein loss) drives the phenotype\n- Locus-specific disruption of looping with locus-specific effect\n- Combinatorial histone-mark perturbation showing direct output dependence\n- Critically: specificity against cell-cycle collapse, global transcriptional collapse, and replication stress must be demonstrated", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Widespread RNA contact, insolubility or body presence does not alone establish mechanical load-bearing necessity.", "Native RNA/protein functional perturbations are positive within their precise contexts; the broad necessity test must separate transcript material from polymerase attachment, splicing, protein recruitment, replication stress and extraction." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Defined RNA compartments, repeat heterochromatin, specialized lncRNA domains and mitotic remodeling are causal in their contexts. They have different outputs, signs and dependencies and cannot be stitched into a single necessary bulk-euchromatin mechanism. Global RNA-chromatin contacts often follow proximity. Local-to-global inference remains Γ, with mapped boundaries preserved rather than fitted to successful responses.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires at least one endogenous perturbation showing the proposed feature contributes causally to the claimed output.", "satisfied": "yes", "supporting_evidence": [ "[12] Efficient MENepsilon/beta depletion disintegrates paraspeckles and prevents recovery after transcription arrest.", "[13] Native RNA-domain deletion maps assembly functions; NONO tether rescue requires its dimerization domain.", "[15] Neat1 loss, including the architectural long isoform, removes paraspeckles in cultured cells and specific adult tissues while baseline viability and examined tissue organization persist." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ε", "requirement_quoted": "Requires context-specific causality with clear scope restriction. Many enhancer, condensate, or accessibility claims belong here.", "satisfied": "yes", "supporting_evidence": [ "[12] Efficient MENepsilon/beta depletion disintegrates paraspeckles and prevents recovery after transcription arrest.", "[13] Native RNA-domain deletion maps assembly functions; NONO tether rescue requires its dimerization domain.", "[15] Neat1 loss, including the architectural long isoform, removes paraspeckles in cultured cells and specific adult tissues while baseline viability and examined tissue organization persist." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Independent causal tests across loci or systems\n- Specificity beyond global transcriptional collapse\n- Narrowing of key alternatives", "satisfied": "yes", "supporting_evidence": [ "[12] Efficient MENepsilon/beta depletion disintegrates paraspeckles and prevents recovery after transcription arrest.", "[13] Native RNA-domain deletion maps assembly functions; NONO tether rescue requires its dimerization domain.", "[15] Neat1 loss, including the architectural long isoform, removes paraspeckles in cultured cells and specific adult tissues while baseline viability and examined tissue organization persist." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Η", "requirement_quoted": "Requires:\n- Robust endogenous causality\n- Reproducibility across loci/cell states within scope\n- Strong evidence that the proposed mechanism is not a downstream correlate", "satisfied": "no", "supporting_evidence": [ "[12] Efficient MENepsilon/beta depletion disintegrates paraspeckles and prevents recovery after transcription arrest.", "[13] Native RNA-domain deletion maps assembly functions; NONO tether rescue requires its dimerization domain.", "[15] Neat1 loss, including the architectural long isoform, removes paraspeckles in cultured cells and specific adult tissues while baseline viability and examined tissue organization persist." ], "what_would_cross_it": "Replicate RNA-specific loss and endogenous-domain rescue across predefined compartments and physiological states, with isoform abundance, RNA stability and interacting protein concentration matched; distinguish body nucleation from global material mechanics." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires at least one endogenous perturbation showing the proposed feature contributes causally to the claimed output.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "A reversible intact-cell RNA-selective perturbation must abolish verified bulk load-bearing interactions and change chromatin rheology/architecture while preserving polymerase, cellular energy, osmotic state and viability; restore the structural RNA without restoring transcriptional work." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires at least one endogenous perturbation showing the proposed feature contributes causally to the claimed output.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Demonstrate the same material dependency across prespecified compartments, gene densities and cell states, using RNA-specific separation-of-function perturbations and orthogonal structure/mechanics rather than pooled proximity maps." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "Nozawa finds gene-rich versus gene-poor differences and little early bulk transcription effect; wild-type, Walker and RGG rescue distinguish functions.", "HNRNPU cellular architecture can be rescued with resistant cDNA; no apparent cell-cycle/senescence changes, but downstream RAD21 redistribution remains.", "Hilbert compares flavopiridol with retained polymerase/transcript actinomycin D and drug washout; a short inhibitor exposure is not equivalent to six-hour depletion in fibroblasts.", "SAP rescue constructs are close to endogenous levels; XIST/Polycomb spatial effects coexist with maintained Xi silencing.", "Neat1 knockout removes local bodies yet examined baseline viability and stomach organization persist; subsequent restricted reproductive effects remain separate.", "Creamer RNase affects permeabilized nuclei; lamins and NUMA remain while SAF-A releases; centrifugation redistributes RNA and multiple proteins together." ], "note": "Local body formation, gene-rich compaction, heterochromatin stabilization or erosion, RNA-dependent enzymatic recruitment and mitotic eviction are separate measurable contexts. They are fixed by species, phase, compartment and molecular intervention before outcome, not by responders. None is automatically a pan-nuclear interphase necessity test." }, "falsification_patterns_met": [ { "pattern": "Global necessity not selectively abolished in examined tests", "evidence": "Local compartment null phenotypes and dynamic protein exchange do not directly falsify the registered dynamic pan-nuclear material. Contrasting microphase/drug and domain results narrow alternatives and scope, rather than establish zero RNA structural contribution.", "downgrade_applied": false } ], "pitfalls_flagged": [ { "pitfall": "Local-to-global scaffold substitution", "where": "NEAT1, Firre, rDNA, repeats and XIST are defined structures, not automatically global euchromatin." }, { "pitfall": "Contact or insolubility treated as mechanical support", "where": "Ligated RNA-DNA edges and extracted SAR fractions do not measure live load bearing." }, { "pitfall": "RNA cleavage assumed to leave transcription intact", "where": "RNase-H ASOs can terminate polymerase; inhibitors differentially retain complexes." }, { "pitfall": "Dynamic exchange equated with no scaffold", "where": "Rapid SAF-A motion challenges static tethers but allows a transient network." } ], "causal_tally_audit": { "tally_claimed_by_document": 3, "tally_after_audit": 3, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 12, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Reports sharing participants, models or instruments are not independent causal lines.", "Pivotal nulls do not earn positive threshold crossings." ] }, "steelman": { "case_one_rung_higher": "One rung above, Δ: Nozawa wild-type/Walker/RGG rescue, early preserved transcription and mapped gene-density boundaries are strong specific positives. Creamer adds rapid physical RNA-protein redistribution and RNA-dependent SAR retention, while Hilbert distinguishes polymerase-retaining from polymerase-releasing inhibition. Together they make structural RNA contribution credible. The blocker is the registered pan-nuclear necessity inference: none selectively removes RNA material in intact cells while preserving polymerase attachment/protein chemistry and restores material-dependent architecture without restoring transcriptional work.", "case_one_rung_lower": "One rung below, Β: global RNA occupancy and insolubility could be proximity or extraction artifacts, and removing RNA often changes transcription. However, functional domain rescue, local architecture perturbations, microphase contrasts and rapid physical manipulations provide mechanistic support beyond correlation. The dynamic global claim is not directly falsified by fast protein exchange; Γ retains its substantive positive evidence.", "which_rejected": "Keep Γ for the global scope and Ζ for defined RNA-dependent compartments. Do not substitute a rigid static matrix for the dynamic claim, or count inhibitor confounds and local physiological nulls as proof that all structural RNA functions are absent.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: Prespecify several intact interphase cell states and gene-rich/poor compartments; reversibly disrupt nascent RNA material interactions without terminating polymerase or changing RNA-protein abundance, assay chromatin mechanics and compaction with orthogonal live methods, and rescue architecture with endogenous-level structural RNA while transcriptional work remains controlled." }, "final_score": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "Moderate reflects evidence density and reproducibility, not the reviewer's access depth and not any belief about correctness: the local RNA-compartment work replicates across cell systems and a mouse null allele, but the global load-bearing claim rests on a small number of structural studies that share multifunctional-protein perturbations and extraction methods, and no intact-cell RNA-selective test has been independently reproduced. High was considered and declined on that narrow, method-correlated base.", "rests_on_non_peer_reviewed_work": false, "rationale": "Scope-matched aggregation gives Γ for the global meshwork (SC2/SC3). Specific RNA-dependent compartment nucleation retains Ζ under its local scope; it cannot carry the whole-interphase requirement. Strong positive RNA-protein structure studies prevent a purely associational dismissal, but no examined live global RNA-selective loss/rescue isolates necessary load-bearing material from the act of transcription or protein functions." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "Specific RNA compartments and RNA-protein perturbations alter structural outcomes, excluding pure co-occurrence at those scopes. Transcription can produce the RNA and upstream organization while RNA interactions feed back on local structure. Universal prevention, initiation and rate limitation are not jointly shown, nor global necessity. Step 5 describes demonstrated local reinforcement/maintenance; it is not confirmation of the pan-nuclear mesh.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "The 2025 SAF-A depletion and domain-rescue work (PMID40493679), 2025 CTCF-RNA local tests (PMID41296854) and 2026 specialized SFPQ assemblies (PMID42425084) are completed mechanistic studies. No verified pending RNA-selective global-mechanics result is claimed.", "justification": "The 2025 SAF-A depletion and domain-rescue work (PMID40493679), 2025 CTCF-RNA local tests (PMID41296854) and 2026 specialized SFPQ assemblies (PMID42425084) are completed mechanistic studies. No verified pending RNA-selective global-mechanics result is claimed." }, "stability": { "value": "Stable", "trigger": "No named verified pending experiment was identified that would predictably move the global grade; a new selective material test could raise it, but a proposed experiment is not an underway result.", "justification": "No named verified pending experiment was identified that would predictably move the global grade; a new selective material test could raise it, but a proposed experiment is not an underway result." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Γ", "gap_in_rungs": null, "value": "Contested", "justification": "No manufactured field consensus or arithmetic gap." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "none assigned", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": true, "new_level": "Γ", "direction": "newly assigned", "what_moved_it": "Fresh primary evidence appraisal; not blinded.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "Prespecify several intact interphase cell states and gene-rich/poor compartments; reversibly disrupt nascent RNA material interactions without terminating polymerase or changing RNA-protein abundance, assay chromatin mechanics and compaction with orthogonal live methods, and rescue architecture with endogenous-level structural RNA while transcriptional work remains controlled.", "readout": "Verified RNA network interaction/load response, chromatin compaction and compartment scale, nascent transcription, energy, stress and cell-cycle state", "critical_control": "RNA-selective versus polymerase-selective perturbation, RNA-binding separation-of-function rescue, matched protein level/ATP/ionic conditions, native isoform and genomic DNA controls, viability and replication stress", "supporting_result": "Loss of verified RNA material interactions precedes global structural change and is specifically rescued by the structural RNA at fixed polymerase/protein state across preregistered contexts", "falsifying_result": "RNA network loss leaves global mechanics intact, or effects follow polymerase termination, osmotic/protein redistribution or stress and are rescued without RNA material" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Develop intact-cell RNA-selective structure perturbations that preserve polymerase attachment and RNA/protein chemistry.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Measure load-bearing rheology independently of RNA occupancy, chromatin marks or extraction insolubility.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Separate seconds/minutes structural responses from later splicing, replication stress and cell-cycle redistribution.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Map gene-density, compartment and developmental boundaries before outcomes rather than define scaffold-active responders.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Reconcile short polymerase-retaining inhibition with longer RNA depletion and cell-type-specific drug responses.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Test RNA rescue without restoring transcriptional work or the deleted DNA regulatory element.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 7", "statement": "Audit linked correction bodies and full supplements; unavailable public body is an access limitation, not a negative experiment.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-12", "reviewer": "Codex", "evidence_base_note": "60 primary reports; literature cutoff 2026-10-09; source examination UTC date 2026-10-12; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. Scite is queried per case where connected; received tallies/outgoing reference contexts are not audited incoming contrasting statements. Tool receipts record actual use. Supplementary discovery outputs do not earn primary-count credit. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded source-based critical review; no complete-paper/supplement audit, independent scientific peer review or blinded calibration. Revision cases retain original prose outside the three framework output blocks and have explicit correction logs." }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "Ranking categorical verdict and index guidance were visible. No completed blinded calibration claimed." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Endogenous RNA depletion and domain editing, mouse alleles, native protein degrons/rescue, inhibitor contrasts, fractionation, mechanical redistribution and RNA-contact maps were considered. They can support upper rungs for defined local structure, without a clinical RCT. Global load-bearing necessity lacks an RNA-selective intact-cell separation-of-function and specific structural rescue. No complementary same-scope convergent case is discarded by reapplying an association cap to one component." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Endogenous RNA depletion and domain editing, mouse alleles, native protein degrons/rescue, inhibitor contrasts, fractionation, mechanical redistribution and RNA-contact maps were considered. They can support upper rungs for defined local structure, without a clinical RCT. Global load-bearing necessity lacks an RNA-selective intact-cell separation-of-function and specific structural rescue. No complementary same-scope convergent case is discarded by reapplying an association cap to one component." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Endogenous RNA depletion and domain editing, mouse alleles, native protein degrons/rescue, inhibitor contrasts, fractionation, mechanical redistribution and RNA-contact maps were considered. They can support upper rungs for defined local structure, without a clinical RCT. Global load-bearing necessity lacks an RNA-selective intact-cell separation-of-function and specific structural rescue. No complementary same-scope convergent case is discarded by reapplying an association cap to one component." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Endogenous RNA depletion and domain editing, mouse alleles, native protein degrons/rescue, inhibitor contrasts, fractionation, mechanical redistribution and RNA-contact maps were considered. They can support upper rungs for defined local structure, without a clinical RCT. Global load-bearing necessity lacks an RNA-selective intact-cell separation-of-function and specific structural rescue. No complementary same-scope convergent case is discarded by reapplying an association cap to one component." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Endogenous RNA depletion and domain editing, mouse alleles, native protein degrons/rescue, inhibitor contrasts, fractionation, mechanical redistribution and RNA-contact maps were considered. They can support upper rungs for defined local structure, without a clinical RCT. Global load-bearing necessity lacks an RNA-selective intact-cell separation-of-function and specific structural rescue. No complementary same-scope convergent case is discarded by reapplying an association cap to one component." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 60, "claims_total": 64, "claims_verified": 64, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 60, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "SAF-A loss compacts gene-rich regions with wild-type but not Walker-A or RGG-deficient rescue; early bulk transcription changes are limited. RNA-sensitive fractionation uses extracted nuclear samples; tagged rescue and selected loci do not isolate a pan-nuclear load-bearing RNA mesh.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph20, 1:Results:paragraph21, 1:Results:paragraph22, 1:Results:paragraph82, 1:Results:paragraph98. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C2", "text": "HNRNPU depletion alters global compaction, LADs, compartments and loops; resistant cDNA rescues cellular architecture with cell-cycle controls. The depleted target is multifunctional protein, not selectively RNA material; RAD21 redistribution and transcriptional changes remain alternative mediators.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Results:paragraph0, 0:Results:paragraph2, 0:Results:paragraph3, 0:Results:paragraph4, 0:Results:paragraph23. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C3", "text": "Transcription-linked RNA-rich pockets segregate from DNA; flavopiridol coarsens domains while actinomycin-D-retained complexes preserve their pattern. Different inhibitors alter polymerase and transcript attachment together; microphase modeling does not uniquely identify a mechanical RNA mesh or force-bearing rheology.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph5, 1:Results:paragraph6, 1:Results:paragraph7, 1:Results:paragraph14. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C4", "text": "RNase-H ASOs cleaving nascent RNA also cause XRN2-mediated polymerase termination. This tests a major RNA-removal confound; it neither selectively abolishes global RNA structure nor proves RNA has no architectural role.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C5", "text": "Near-endogenous rescue alleles separate dynamic SAP-dependent XIST localization from global RNA expression and retained maintenance-phase Xi silencing. Rapid FRAP disproves a stable tether interpretation, not a transient load-bearing network; XIST compartment and ordinary euchromatin are different scopes.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph11, 1:Results:paragraph12, 1:Results:paragraph13, 1:Results:paragraph20, 1:Results:paragraph23. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C6", "text": "Aurora-B-dependent RNA eviction from chromosomes is required for normal mitotic segregation. Prophase/nuclear-envelope breakdown is outside registered interphase bulk-euchromatin scope; cell-cycle material remodeling is not pan-nuclear interphase necessity.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C7", "text": "Firre locus loss or hnRNPU reduction decreases specific cross-chromosomal colocalization and alters focal RNA localization. Whole-locus deletion, growth changes and no RNA-only local rescue limit attribution to transcript rather than DNA/transcription; selected trans sites are not global scaffolding.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:RESULTS:paragraph8, 1:RESULTS:paragraph10, 1:RESULTS:paragraph15, 1:RESULTS:paragraph16, 1:RESULTS:paragraph17. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C8", "text": "LINE1 RNA recruits nucleolin and KAP1 for Dux repression and rDNA expression in early-development contexts. Specific regulatory recruitment and self-renewal do not show all interphase euchromatin requires an open mechanical mesh.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C9", "text": "SAFB-repeat RNA interactions support heterochromatin foci and genomic compartmentalization. SAFB differs from SAF-A; compact heterochromatin is a distinct output from universal RNA-driven decompaction; phase-specific loss/rescue needs deeper access.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C10", "text": "LINE1 RNA accumulation inhibits SUV39H1 activity; RNA reduction restores heterochromatin and improves restricted mouse phenotypes. Pathological RNA abundance can erode heterochromatin; chromatin marks and progeroid context do not identify a universal physical scaffold.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C11", "text": "HNRNPU loss reduces Polycomb marks across Airn/Kcnq1ot1 domains with distinct effects while their chromatin localization and PRC1 association persist. Protein recruitment, RNA abundance and chromatin modification differ by domain; repressive multimegabase regulation is not global open-euchromatin support.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C12", "text": "Efficient MENepsilon/beta depletion disintegrates paraspeckles and prevents recovery after transcription arrest. Long NEAT1 isoform and specific RNA-protein compartment are targeted; public body unavailable, so perturbation detail beyond original abstract remains limited.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C13", "text": "Native RNA-domain deletion maps assembly functions; NONO tether rescue requires its dimerization domain. Synthetic rescue and in-vitro aggregation do not alone prove endogenous liquid-state mechanics; public body unavailable, complete original abstract examined.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C14", "text": "RNA terminal-domain deletions alter paraspeckle shell organization and support an experimentally tested micelle model. Shape-prediction agreement does not demonstrate one physics for every nuclear body; public body unavailable in this run.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C15", "text": "Neat1 loss, including the architectural long isoform, removes paraspeckles in cultured cells and specific adult tissues while baseline viability and examined tissue organization persist. Compartment assembly necessity is real, but ordinary-laboratory absence of gross phenotype does not rule out stress or reproductive functions.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Results and discussion:paragraph5, 1:Results and discussion:paragraph9, 1:Results and discussion:paragraph11, 1:Results and discussion:paragraph12, 1:Results and discussion:paragraph16. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C16", "text": "RBM14 and FUS low-complexity domains are required for rescue of paraspeckle formation. Protein domain necessity identifies cooperating scaffold chemistry, not solely RNA mechanics or a pan-nuclear matrix.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C17", "text": "A defined paraspeckle compartment contains dynamic RNA-binding proteins and reorganizes during transcription inhibition. Protein localization and dynamics establish the body but not RNA-specific necessity or global chromatin mechanics.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C18", "text": "Distinct NEAT1 RNA regions interact with p54nrb. Binding-site identification alone does not prove compartment assembly necessity or sufficient endogenous architecture.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C19", "text": "PSP1 dimer interaction and RNA-binding domain contribute to localization; bodies return when transcription resumes. Transcription reactivation changes RNA and machinery together; protein-targeting controls do not identify global RNA load bearing.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C20", "text": "NONO/PSPC1 dimer structure and coiled-coil mutants support higher-order paraspeckle organization. Crystal structure and mutant targeting remain local protein assembly evidence, not in-situ RNA network mechanics.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C21", "text": "NEAT1 sequence folding and RNA-RNA interactions offer potential scaffold architecture. Predicted or in-vitro structure is not a direct endogenous force-bearing or assembly perturbation.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C22", "text": "Neat1 and p54nrb support CARM1 localization, methylation and early embryonic progression. Transient embryo depletion and reciprocal factor effects are context specific, not proof of a universal adult interphase mesh.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C23", "text": "Ctn RNA remains nuclear-retained without intact paraspeckles but redistributes into residual and perinucleolar foci. Paraspeckles influence local partitioning, while nuclear retention persists through other mechanisms.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C24", "text": "Some knockout females fail corpus-luteum formation; ovarian transplant or progesterone partially rescues fertility. The enabling suboptimal condition is unmeasured; a responder-defined scope is not acceptable, and endocrine rescue does not isolate physical scaffolding.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C25", "text": "Two abundant lncRNAs occupy many active sites with distinct patterns responsive to transcription. Widespread occupancy responds to activity and is not proof that RNA structurally supports all occupied DNA.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C26", "text": "RNA-binding proteins enrich at promoters; RBM25 loss affects YY1 binding, looping and transcription. Multifunctional protein dependence and hotspots do not identify a mechanical pan-nuclear RNA network.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C27", "text": "Global RNA-chromatin contacts concentrate at active promoters and enhancers. Proximity ligation and nascent transcription create contact signal; map connectivity is not RNA material necessity.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C28", "text": "Genome-wide RNA-contact mapping identifies cell-state-specific patterns with reduced nascent-transcription bias. Intact-nuclear proximity ligation does not determine load bearing; linked correction details are unexamined.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C29", "text": "RNA-DNA ligation maps widespread endogenous transcript associations and distal contacts. Cross-species control narrows ligation errors but cannot establish mechanical necessity; linked erratum remains attached.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C30", "text": "Most ncRNA contacts follow three-dimensional proximity, and expression changes are unlikely explained by one ncRNA. This opposes treating every proximity edge as specific RNA-guided control; it does not exclude collective or local scaffold effects.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C31", "text": "Endogenous RNAs show focal occupancy and distinct regulatory targeting patterns. Three specialized RNAs and mapping assays do not license a uniform genome-wide mesh; local gene regulation is not material mechanics.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C32", "text": "SWI/SNF component loss disrupts NEAT1 and satellite-III bodies while BRG1 ATPase mutation retains paraspeckle integrity. Noncanonical protein assembly supports RNA-dependent local bodies; complete abstract access only, no native ATPase-body paragraph audit.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C33", "text": "NEAT1-ARID1B interactions connect paraspeckles with transcription and splicing regulation. Shared target expression and protein interactions are not pan-nuclear physical scaffold or phase-state-specific necessity.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C34", "text": "Neat1 modulates PRC2 binding between transcripts and bivalent promoters during cell-state transition. Selective regulatory redistribution is different from universally propping open bulk euchromatin.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C35", "text": "Cytoplasmic stress-granule formation promotes stress-induced paraspeckle assembly. Stress-dependent protein sequestration changes local body abundance; nuclear/cytoplasmic crosstalk is not global interphase scaffold proof.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C36", "text": "RNA-binding-dependent BAZ2A bodies protect nearby repressive compartments; RNA affinity changes spatial behavior. Weak and strong RNA binders have different effects; protein/phase specificity and whole-genome generalization are not settled by body presence.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C37", "text": "RNA stabilizes SUV39H1 at constitutive heterochromatin, with nucleic-acid-binding mutants altering function. Nucleic-acid specificity, RNAse/extraction and polymerase effects remain; heterochromatin maintenance differs from open euchromatin.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C38", "text": "A pRNA stem-loop is required for TIP5 targeting and ribosomal-gene silencing. Specific RNA-protein recruitment to rDNA does not establish a pervasive physical nuclear mesh.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C39", "text": "TIP5 acetylation changes pRNA binding and heterochromatic ribosomal-gene state. Protein modification and metabolic feedback identify local regulation, not bulk decompaction.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C40", "text": "Evf2 recruits and inhibits BRG1 remodeling at defined regulatory sites. Promiscuous RNA binding and enzymatic inhibition can affect chromatin without RNA acting as a load-bearing scaffold.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C41", "text": "Nascent RNA contributes to elongation-factor and kinase recruitment to genes. Nonmammalian transcriptional recruitment is an alternative RNA function, not global mammalian interphase mechanics.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C42", "text": "Transcribed retroviral loci recruit RNA-associated TET2 for transcriptional and RNA regulation. Sequence/state-specific recruitment and RNA modification differ from a universal structural armature.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C43", "text": "RNA competes with chromatin for Mi-2/CHD4 binding and nucleosome remodeling. A protective RNA effect can be biochemical competition rather than force-bearing structure; drug and digestion controls do not isolate a mesh.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C44", "text": "Repeat-derived siRNA mimics rescue Dcr2-deficient heterochromatin and segregation defects. RNAi silencing and nonmammalian pericentric heterochromatin are distinct from nascent RNA bulk-euchromatin scaffold.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C45", "text": "SAF-A binds DNA and RNA at differing affinities and can form higher-order complexes. Binding and isolated complexes motivate architecture without a selective endogenous necessity test.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C46", "text": "SAF-A localization varies across interphase, centromeres and chromosome surfaces. Fixed antibodies and tagged protein networks do not identify load-bearing mechanics; cell-cycle distribution matters.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C47", "text": "Dual protein loss abolishes Pol-II transcription while Pol-I transcription remains. Global transcription collapse prevents isolating a specific scaffold state; interaction can occur without mRNA.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C48", "text": "SAF-A supports Oct4 expression and regulatory complexes in pluripotent cells. Promoter and transcription-factor activity provide protein functions independent of an RNA mesh; overexpression rescue retains its scope.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C49", "text": "Damage triggers recruitment then exclusion of RNA-biogenesis factors from transcribed chromatin. DNA damage and R-loop resolution can change scaffold localization without testing ordinary interphase architecture.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C50", "text": "Protein loss alters licensing, fork progression and timing while damage/quiescence increase. Replication stress and cell-state changes are major alternative causes of later chromatin phenotypes.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C51", "text": "Mutant cis sequence changes hnRNPU affinity and long-range Shh regulation. RNA-specific scaffold contribution is not isolated; inferred matrix relocation at one mutant locus cannot generalize globally.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C52", "text": "Protein loss disrupts accessibility and sensitizes liver to injury through truncated TrkB signaling. Protein, splicing/signaling and disease stress can explain effects; model does not directly remove structural RNA.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C53", "text": "Alpha-satellite RNAs support SAF-A return after mitosis, lamina reassembly and accurate segregation. Mitotic exit and centromeric RNA are specialized contexts, not continuous necessity throughout all interphase chromatin.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C54", "text": "Ubiquitinated hnRNPU associates with CTCF/cohesin and alters measured condensation. Cell-cycle regulator and protein-interaction changes do not isolate RNA material or rule out cell-state redistribution.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C55", "text": "NONO protein allosterically activates NSD1 and contributes to differentiation. Paraspeckle-protein dependence can be protein-protein catalysis; RNA scaffold or body necessity was not isolated.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C56", "text": "RNA-dependent SFPQ assemblies support extra-long gene expression and splicing. Defined long-gene complexes and multifunctional protein perturbation are not evidence of a pervasive interphase mesh.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C57", "text": "Local Pvt1 RNA level shortens Myc burst duration; premature termination increases output and tumor phenotypes. Termination changes the act of transcription and RNA abundance; local feedback does not show genome-wide mechanical decompaction.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C58", "text": "CTCF ZF1 and selected RNAs contribute to cell-specific loops and gene regulation. Protein domain and transcript-truncation effects require chemistry/transcription controls; loop specificity does not establish pan-nuclear scaffolding.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C59", "text": "Multiposition RNA labeling resolves heterogeneous paraspeckle organization and surface RNA configurations. Particle averaging and morphology identify local structure, not a causal whole-nucleus load-bearing requirement.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C60", "text": "Repeat-rich nascent RNA persists in extracted scaffold; rapid centrifugation redistributes RNA/proteins with compaction, and RNase ablates scaffold attachment enrichment. Strong physical support, but centrifugation redistributes several materials and RNase tests permeabilized/extracted nuclei; selective live RNA load-bearing necessity remains unresolved.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 60 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:RESULTS:paragraph0, 1:RESULTS:paragraph3, 1:RESULTS:paragraph4, 1:RESULTS:paragraph10, 1:RESULTS:paragraph22, 1:RESULTS:paragraph27, 1:RESULTS:paragraph28, 1:RESULTS:paragraph29, 1:RESULTS:paragraph33. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC1", "text": "For defined NEAT1-dependent paraspeckle assembly, RNA depletion, mouse genetic loss and endogenous RNA-domain editing/rescue provide complementary causal support across cellular and animal systems. These justify Ζ for the existential subclaim that specific RNAs nucleate defined compartments; they do not establish equivalent necessity/sufficiency for every XIST, MATR3 or LINE1 example, every RNA body, or endogenous liquid-phase physics. Those separate local mechanisms retain source-specific boundaries.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 42, 44, 48, 51, 55, 56, 57, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC2", "text": "SAF-A perturbation/rescue, regional compaction and transcription/RNA-linked microphase studies provide substantial mechanistic evidence, while repeat-rich scaffold extraction and rapid physical redistribution strengthen a physical contribution. However, global protein loss, polymerase/RNA attachment, transcription termination and permeabilized RNase do not selectively isolate a necessary pan-nuclear RNA material in intact interphase cells. The global load-bearing requirement remains Γ; narrow RNA-protein architecture contributions are not denied.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 25, 26, 27, 28, 29, 30, 36, 41, 43, 45, 46, 47, 49, 50, 52, 53, 54, 60 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC3", "text": "Defined RNA compartments, repeat heterochromatin, specialized lncRNA domains and mitotic remodeling are causal in their contexts. They have different outputs, signs and dependencies and cannot be stitched into a single necessary bulk-euchromatin mechanism. Global RNA-chromatin contacts often follow proximity. Local-to-global inference remains Γ, with mapped boundaries preserved rather than fitted to successful responses.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 34, 35, 36, 37, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CH", "text": "Specific RNAs build nuclear compartments, while a necessary pan-nuclear RNA mesh remains supported incompletely and requires a more selective material test.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 3, 15, 60, 5, 4 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-12", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Nozawa RS, Boteva L, Soares DC et al. 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Nucleic acids research. 2018.", "tier": "A", "kind": "primary", "pmid": "29394378", "doi": "10.1093/nar/gky046", "url": "https://pubmed.ncbi.nlm.nih.gov/29394378/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID29394378", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C21", "CSC1" ] }, { "n": 22, "citation": "Hupalowska A, Jedrusik A, Zhu M et al. CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development. 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Development (Cambridge, England). 2014.", "tier": "A", "kind": "primary", "pmid": "25359727", "doi": "10.1242/dev.110544", "url": "https://pubmed.ncbi.nlm.nih.gov/25359727/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25359727", "access_depth": "abstract_metadata", "access_note": "Complete original abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C24", "CSC1", "CSC3" ] }, { "n": 25, "citation": "West JA, Davis CP, Sunwoo H et al. The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites. 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No complete-paper or supplement audit claimed.", "carries_claims": [ "C60", "CSC2", "CSC3", "CH" ] } ], "independence_basis": { "required": true, "lines": [ { "label": "RNA-specific local loss and genetic structure", "sources": [ 12, 15 ], "excludes_error": "Transcript reduction versus animal genomic allele/body loss narrow an antisense-only or culture-only error; allele cis effects and residual isoforms still require care." }, { "label": "Local assembly-domain rescue", "sources": [ 13, 16, 32 ], "excludes_error": "RNA domain and cooperating protein architecture tests narrow generic protein/RNA abundance explanations; shared paraspeckle systems are not five independent global mesh confirmations." }, { "label": "Intact chromatin and protein separation", "sources": [ 1, 2, 5 ], "excludes_error": "Mutant/cDNA rescue and dynamic domains narrow off-target protein loss; they still share multifunctional protein inference for global RNA material." }, { "label": "Transcriptional and extracted physical contrasts", "sources": [ 3, 60, 4 ], "excludes_error": "Different inhibitor behavior, extracted SAR sensitivity and RNA-cleavage termination expose distinct confounds, without a single selective live global RNA test." } ], "shared_failure_mode_checked": true, "note": "Count studies and failure modes rather than papers or species. Several paraspeckle domain papers share genetic platforms and molecular assembly assumptions; NEAT1 knockout tissue/MEF measurements are one study. Mapping methods differ in ligation bias but none tests load bearing. SAF-A loss in different cells is not automatically independent validation of an RNA-specific material dependency. Local SC1 convergence does not count as global SC2 convergence." }, "consensus_validation": { "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/noncoding-rna-euchromatin-architecture/E1nqK_4kT96eLC2AHw53-Q/" ], "query_record_note": "Exact visible question/response retained privately in raw browser receipt.", "primary_comparison_count": 9, "primary_comparisons": [ { "pmid": "28622508", "doi": "10.1016/j.cell.2017.05.029", "source_type": "primary study report", "study_group": "PMID28622508", "access_depth": "full_text_partial", "consensus_aspect": "Missing original SAF-A separation-of-function positives", "result_comparison": "Consensus could not retrieve Nozawa's exact paper and its headline understated the positive mechanistic case. Original Results show gene-rich compaction, earlier structural than nuclear-area change, little early bulk transcription change, and wild-type/Walker/RGG rescue differences. Its RNase test uses extracted nuclear samples. This supports a scoped RNA-protein structure contribution while leaving selective global RNA necessity unresolved.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/28622508/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\28622508-s1-p0-20-21-22-82-98.json", "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\28622508-s1-p98.json" ] }, { "pmid": "29273625", "doi": "10.1101/gr.224576.117", "source_type": "primary study report", "study_group": "PMID29273625", "access_depth": "full_text_partial", "consensus_aspect": "HNRNPU hepatocyte architecture is not the SAFB satellite study", "result_comparison": "Consensus marked the exact HNRNPU paper unavailable and substituted Huo's SAFB heterochromatin result. The original hepatocyte paper uses two shRNAs and resistant cDNA rescue, reports architecture changes without apparent cell-cycle/senescence shift, and later RAD21 redistribution. HNRNPU/SAF-A and SAFB are different proteins, and global protein depletion is not selective RNA-mesh removal.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/29273625/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\29273625-s0-p0-2-3-4-23.json" ] }, { "pmid": "33649325", "doi": "10.1038/s41467-021-21589-3", "source_type": "primary study report", "study_group": "PMID33649325", "access_depth": "full_text_partial", "consensus_aspect": "RNA amount and attached transcribing complexes differ", "result_comparison": "Original microphase Results show flavopiridol-associated coarsening despite high retained nuclear RNA, while briefly arrested polymerase with its transcripts after actinomycin D preserves the pattern. Drug washout reverses coarsening and mouse ESCs provide a second tested cell context. These results support a dynamic RNA/polymerase-tether contribution, not a demonstration that dynamic organization excludes every load-bearing network.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33649325/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\33649325-s1-p2-5-6-7-14.json" ] }, { "pmid": "34320406", "doi": "10.1016/j.molcel.2021.07.004", "source_type": "primary study report", "study_group": "PMID34320406", "access_depth": "full_text_partial", "consensus_aspect": "Original physical scaffold study strengthens the positive case", "result_comparison": "Consensus helped identify Creamer's original paper, which was fetched and examined independently. Original Results confirm that stringent extraction releases most nuclear RNA, RNA-sensitive SAF-A and SAR retention, and rapid centrifugation-induced redistribution of RNA/proteins with chromatin compaction. The paper explicitly retains direct-versus-indirect RNase uncertainty. Extracted/permeabilized digestion and simultaneous displacement of several materials cannot by themselves establish selective live RNA necessity, but this is positive physical evidence rather than proof against a structural contribution.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/34320406/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-59-60-6500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\34320406-s1-p0-3-4-10-22-27-28-29-33.json" ] }, { "pmid": "21444682", "doi": "10.1083/jcb.201011110", "source_type": "primary study report", "study_group": "PMID21444682", "access_depth": "full_text_partial", "consensus_aspect": "Local body necessity survives baseline animal viability", "result_comparison": "Consensus did not retrieve this exact mouse paper. Original body examination confirms absent Neat1, including the long NEAT1_2 isoform, and absent paraspeckles in selected tissues, while baseline viability and examined stomach differentiation/organization persist. This verifies local architectural necessity with a biological boundary, not a global RNA-mesh deletion or absence of every physiological RNA function.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/21444682/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\21444682-s1-p5-9-11-12-16.json" ] }, { "pmid": "29932899", "doi": "10.1016/j.molcel.2018.05.019", "source_type": "primary study report", "study_group": "PMID29932899", "access_depth": "abstract_metadata", "consensus_aspect": "Exact RNA domains differ from a substituted review", "result_comparison": "Consensus substituted a Hirose review for direct exact-paper validation. The original complete abstract describes endogenous NEAT1 domain deletions and NONO tether rescue with dimerization dependence. No public original body was obtained this run, so these details are recorded at abstract depth. The local assembly result does not automatically establish the same mechanics across all nuclei.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/29932899/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [] }, { "pmid": "40493679", "doi": "10.1371/journal.pgen.1011719", "source_type": "primary study report", "study_group": "PMID40493679", "access_depth": "full_text_partial", "consensus_aspect": "Dynamic SAF-A does not alone refute transient scaffolding", "result_comparison": "Consensus could not retrieve the final 2025 paper. Original Results use endogenous depletion and rescue constructs close to endogenous levels, identify rapid mobility and compartment-specific SAP effects, and show maintained Xi silencing despite XIST/Polycomb organization changes. This challenges stable tether interpretations; it is not proof that rapidly exchanging networks cannot bear load.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/40493679/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\body-presentation-receipts\\40493679-s1-p0-1-11-12-13-20-23.json" ] }, { "pmid": "31924447", "doi": "10.1016/j.molcel.2019.12.029", "source_type": "primary study report", "study_group": "PMID31924447", "access_depth": "abstract_metadata", "consensus_aspect": "Nascent RNA cleavage changes polymerase termination", "result_comparison": "The original complete abstract shows RNase-H ASOs cause XRN2-mediated Pol-II termination in cells and mice. Consensus did not directly validate this requested result. A depletion experiment must therefore distinguish loss of RNA material from loss of attached polymerase/transcriptional activity; no original body access is claimed.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/31924447/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [] }, { "pmid": "33053167", "doi": "10.1083/jcb.201910148", "source_type": "primary study report", "study_group": "PMID33053167", "access_depth": "abstract_metadata", "consensus_aspect": "Mitotic RNA eviction has a separate scope", "result_comparison": "The original abstract identifies Aurora-B-mediated SAF-A phosphorylation and RNA eviction during prophase, with segregation defects when the pathway fails. Consensus did not retrieve the exact paper. Mitotic condensation and envelope breakdown are specialized states, so this result cannot be imported as pan-nuclear interphase necessity.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33053167/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\examinations\\original-0-20-6500.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_remaining_priority_16_19_2026-10-12\\rna-scaffold\\consensus-browser-2026-10-12.json", "sha256": "6a66b249b7476b560549ddf2e883def2a5e1130a9daadc556fce6ee58598f1d1" } ], "independent_blinded_audit": false, "cutoff": "2026-10-09", "completed_utc": "2026-10-12T20:11:20.375892+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }