Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction

Mol Cell. 2021 Sep 2;81(17):3509-3525.e5. doi: 10.1016/j.molcel.2021.07.004. Epub 2021 Jul 27.


Nuclear chromosomes transcribe far more RNA than required to encode protein. Here we investigate whether non-coding RNA broadly contributes to cytological-scale chromosome territory architecture. We develop a procedure that depletes soluble proteins, chromatin, and most nuclear RNA from the nucleus but does not delocalize XIST, a known architectural RNA, from an insoluble chromosome "scaffold." RNA-seq analysis reveals that most RNA in the nuclear scaffold is repeat-rich, non-coding, and derived predominantly from introns of nascent transcripts. Insoluble, repeat-rich (C0T-1) RNA co-distributes with known scaffold proteins including scaffold attachment factor A (SAF-A), and distribution of these components inversely correlates with chromatin compaction in normal and experimentally manipulated nuclei. We further show that RNA is required for SAF-A to interact with chromatin and for enrichment of structurally embedded "scaffold attachment regions" prevalent in euchromatin. Collectively, the results indicate that long nascent transcripts contribute a dynamic structural role that promotes the open architecture of active chromosome territories.

Keywords: HNRNPU; NUMA; SAF-A; XIST; chromatin-associated RNA; nascent RNA; nuclear matrix; nuclear scaffold; nucleus; scaffold-attachment regions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / physiology
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromosomes / genetics
  • Chromosomes / metabolism
  • Euchromatin / metabolism
  • Humans
  • Mice
  • Nuclear Matrix / genetics
  • Nuclear Matrix / metabolism*
  • RNA / genetics
  • RNA / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Transcription, Genetic / genetics


  • Chromatin
  • Euchromatin
  • RNA, Long Noncoding
  • RNA, Untranslated
  • RNA