{
  "cutoff": "2026-10-09",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "19188602",
      "year": "2009",
      "title": "MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles.",
      "doi": "10.1073/pnas.0807899106",
      "url": "https://pubmed.ncbi.nlm.nih.gov/19188602/",
      "interpretation": "RNA depletion establishes defined paraspeckle architectural dependence."
    },
    {
      "pmid": "21444682",
      "year": "2011",
      "title": "Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice.",
      "doi": "10.1083/jcb.201011110",
      "url": "https://pubmed.ncbi.nlm.nih.gov/21444682/",
      "interpretation": "Mouse genetic loss removes local bodies with baseline tissue boundaries."
    },
    {
      "pmid": "24463464",
      "year": "2014",
      "title": "Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre.",
      "doi": "10.1038/nsmb.2764",
      "url": "https://pubmed.ncbi.nlm.nih.gov/24463464/",
      "interpretation": "Firre locus and protein perturbations test selected trans-site organization."
    },
    {
      "pmid": "28622508",
      "year": "2017",
      "title": "SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.",
      "doi": "10.1016/j.cell.2017.05.029",
      "url": "https://pubmed.ncbi.nlm.nih.gov/28622508/",
      "interpretation": "SAF-A RNA-binding/oligomer rescue links structure to gene-rich chromatin."
    },
    {
      "pmid": "29273625",
      "year": "2018",
      "title": "The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes.",
      "doi": "10.1101/gr.224576.117",
      "url": "https://pubmed.ncbi.nlm.nih.gov/29273625/",
      "interpretation": "HNRNPU perturbation changes broader cellular genome architecture."
    },
    {
      "pmid": "33649325",
      "year": "2021",
      "title": "Transcription organizes euchromatin via microphase separation.",
      "doi": "10.1038/s41467-021-21589-3",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33649325/",
      "interpretation": "Polymerase-retaining versus releasing inhibition tests euchromatin microphases."
    },
    {
      "pmid": "34320406",
      "year": "2021",
      "title": "Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.",
      "doi": "10.1016/j.molcel.2021.07.004",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34320406/",
      "interpretation": "Repeat-rich RNA scaffold extraction and physical redistribution strengthen material hypotheses."
    },
    {
      "pmid": "40493679",
      "year": "2025",
      "title": "Role of the SAF-A/HNRNPU SAP domain in X chromosome inactivation, nuclear dynamics, transcription, splicing, and cell proliferation.",
      "doi": "10.1371/journal.pgen.1011719",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40493679/",
      "interpretation": "Final SAP-domain study separates dynamic nuclear and XIST functions."
    }
  ],
  "gaps": [
    "Develop intact-cell RNA-selective structure perturbations that preserve polymerase attachment and RNA/protein chemistry.",
    "Measure load-bearing rheology independently of RNA occupancy, chromatin marks or extraction insolubility.",
    "Separate seconds/minutes structural responses from later splicing, replication stress and cell-cycle redistribution.",
    "Map gene-density, compartment and developmental boundaries before outcomes rather than define scaffold-active responders.",
    "Reconcile short polymerase-retaining inhibition with longer RNA depletion and cell-type-specific drug responses.",
    "Test RNA rescue without restoring transcriptional work or the deleted DNA regulatory element.",
    "Audit linked correction bodies and full supplements; unavailable public body is an access limitation, not a negative experiment."
  ],
  "decisive_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."
}