Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction
Department of Neurology; Lawrence Lab
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Nucleic Acids, Nucleotides, and Nucleosides
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.
HNRNPU, NUMA, SAF-A, XIST, chromatin-associated RNA, nascent RNA, nuclear matrix, nuclear scaffold, nucleus, scaffold-attachment regions
DOI of Published Version
Creamer KM, Kolpa HJ, Lawrence JB. 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. PMID: 34320406; PMCID: PMC8419111. Link to article on publisher's site
Creamer K, Kolpa HJ, Lawrence JB. (2021). Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1016/j.molcel.2021.07.004. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2138