title: Coding RNAs with a non-coding function: maintenance of open chromatin structure.
abstract: The multi-layered organization of the genome in a large nucleoprotein complex termed chromatin regulates nuclear functions by establishing subcompartments with distinct DNA-associated activities. Here, we demonstrate that RNA plays an important role in maintaining a decondensed and biologically active interphase chromatin conformation in human and mouse cell lines. As shown by RNase A microinjection and fluorescence microscopy imaging, digestion of single-stranded RNAs induced a distinct micrometer scale chromatin aggregation of these decondensed regions. In contrast, pericentric heterochromatin was more resistant to RNase A treatment. We identified a class of coding RNA transcripts that are responsible for this activity, and thus termed these 'chromatin-interlinking' RNAs or ciRNAs. The initial chromatin distribution could be restored after RNase A treatment with a purified nuclear RNA fraction that was analyzed by high-throughput sequencing. It comprised long > 500 nucleotides (nt) RNA polymerase II (RNAP II) transcripts that were spliced, depleted of polyadenylation and was enriched with long 3'-untranslated regions (3'-UTRs) above ~800 nt in length. Furthermore, similar reversible changes of the chromatin conformation and the RNAP II distribution were induced by either RNA depletion or RNAP II inhibition. Based on these results we propose that ciRNAs could act as genome organizing architectural factors of actively transcribed chromatin compartments.
authors: Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors: Maïwen
authors: M
authors: Caudron-Herger
authors: Katharina
authors: K
authors: Müller-Ott
authors: Jan-Philipp
authors: JP
authors: Mallm
authors: Caroline
authors: C
authors: Marth
authors: Ute
authors: U
authors: Schmidt
authors: Katalin
authors: K
authors: Fejes-Tóth
authors: Karsten
authors: K
authors: Rippe
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure*; D006801:Humans; D007399:Interphase; D051379:Mice; D008856:Microscopy, Fluorescence; D012313:RNA / Q000378:metabolism* / Q000502:physiology; D012319:RNA Polymerase II / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism* / Q000502:physiology; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D002843:Chromatin; D012342:RNA, Small Nuclear; D022661:RNA, Untranslated; D012313:RNA; D012319:RNA Polymerase II; D012259:Ribonuclease, Pancreatic