1. RNA promotes the formation of spatial compartments in the nucleus
- Author
-
Quinodoz, Sofia A, Jachowicz, Joanna W, Bhat, Prashant, Ollikainen, Noah, Banerjee, Abhik K, Goronzy, Isabel N, Blanco, Mario R, Chovanec, Peter, Chow, Amy, Markaki, Yolanda, Thai, Jasmine, Plath, Kathrin, and Guttman, Mitchell
- Subjects
Genetics ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Animals ,Cell Nucleus ,Chromobox Protein Homolog 5 ,Chromosomes ,DNA ,DNA ,Satellite ,DNA-Binding Proteins ,Dactinomycin ,Female ,Genome ,HEK293 Cells ,Heterochromatin ,Humans ,Mice ,Models ,Biological ,Multigene Family ,RNA ,RNA Polymerase II ,RNA Processing ,Post-Transcriptional ,RNA Splicing ,RNA ,Long Noncoding ,RNA ,Messenger ,RNA ,Ribosomal ,RNA-Binding Proteins ,Transcription ,Genetic ,RNA processing ,cajal bodies ,chromocenters ,histone locus bodies ,lncRNAs ,ncRNAs ,nuclear bodies ,nuclear structure ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
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.
- Published
- 2021