RNA promotes the formation of spatial compartments in the nucleus

Cell. 2021 Nov 11;184(23):5775-5790.e30. doi: 10.1016/j.cell.2021.10.014. Epub 2021 Nov 4.


RNA, DNA, and protein molecules are highly organized within three-dimensional (3D) structures in the nucleus. Although RNA has been proposed to play a role in nuclear organization, exploring this has been challenging because existing methods cannot measure higher-order RNA and DNA contacts within 3D structures. To address this, we developed RNA & DNA SPRITE (RD-SPRITE) to comprehensively map the spatial organization of RNA and DNA. These maps reveal higher-order RNA-chromatin structures associated with three major classes of nuclear function: RNA processing, heterochromatin assembly, and gene regulation. These data demonstrate that hundreds of ncRNAs form high-concentration territories throughout the nucleus, that specific RNAs are required to recruit various regulators into these territories, and that these RNAs can shape long-range DNA contacts, heterochromatin assembly, and gene expression. These results demonstrate a mechanism where RNAs form high-concentration territories, bind to diffusible regulators, and guide them into compartments to regulate essential nuclear functions.

Keywords: RNA processing; cajal bodies; chromocenters; histone locus bodies; lncRNAs; ncRNAs; nuclear bodies; nuclear structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Chromobox Protein Homolog 5 / metabolism
  • Chromosomes / metabolism
  • DNA / metabolism
  • DNA, Satellite / metabolism
  • DNA-Binding Proteins / metabolism
  • Dactinomycin / pharmacology
  • Female
  • Genome
  • HEK293 Cells
  • Heterochromatin / metabolism
  • Humans
  • Mice
  • Models, Biological
  • Multigene Family
  • RNA / metabolism*
  • RNA Polymerase II / metabolism
  • RNA Processing, Post-Transcriptional / drug effects
  • RNA Processing, Post-Transcriptional / genetics
  • RNA Splicing / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Ribosomal / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription, Genetic / drug effects


  • DNA, Satellite
  • DNA-Binding Proteins
  • Heterochromatin
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Ribosomal
  • RNA-Binding Proteins
  • Spen protein, mouse
  • Chromobox Protein Homolog 5
  • Dactinomycin
  • RNA
  • DNA
  • RNA Polymerase II