A functional link between nuclear RNA decay and transcriptional control mediated by the polycomb repressive complex 2 Journal Article

Authors: Garland, W.; Comet, I.; Wu, M.; Radzisheuskaya, A.; Rib, L.; Vitting-Seerup, K.; Lloret-Llinares, M.; Sandelin, A.; Helin, K.; Jensen, T. H.
Article Title: A functional link between nuclear RNA decay and transcriptional control mediated by the polycomb repressive complex 2
Abstract: ZFC3H1 targets pA+ RNA for decay by the nuclear RNA exosome. Garland et al. report a disruptive relationship between excess RNA and PRC2 upon depletion of ZFC3H1 in mouse ESCs. In such conditions, RNA is bound by PRC2 components, which show reduced binding to chromatin and fellow PRC2 proteins. © 2019 The Author(s) Pluripotent embryonic stem cells (ESCs) constitute an essential cellular niche sustained by epigenomic and transcriptional regulation. Any role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the poly(A) RNA exosome targeting (PAXT) connection, and transcriptional control by the polycomb repressive complex 2 (PRC2). Knockout of the PAXT component ZFC3H1 impairs mouse ESC differentiation. In addition to the upregulation of bona fide PAXT substrates, Zfc3h1−/− cells abnormally express developmental genes usually repressed by PRC2. Such de-repression is paralleled by decreased PRC2 binding to chromatin and low PRC2-directed H3K27 methylation. PRC2 complex stability is compromised in Zfc3h1−/− cells with elevated levels of unspecific RNA bound to PRC2 components. We propose that excess RNA hampers PRC2 function through its sequestration from DNA. Our results highlight the importance of balancing nuclear RNA levels and demonstrate the capacity of bulk RNA to regulate chromatin-associated proteins. © 2019 The Author(s)
Keywords: controlled study; methylation; nonhuman; protein function; animal cell; mouse; gene targeting; animal experiment; protein stability; cell differentiation; gene expression regulation; transcription regulation; chromatin; gene repression; gene control; upregulation; developmental gene; nuclear rna; embryoid body; prc2; polycomb repressive complex 2; male; priority journal; article; mouse embryonic stem cell; rna exosome; h3k27 methylation; nuclear rna decay; paxt; stem cell regulation
Journal Title: Cell Reports
Volume: 29
Issue: 7
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2019-11-12
Start Page: 1800
End Page: 1811.e6
Language: English
DOI: 10.1016/j.celrep.2019.10.011
PUBMED: 31722198
PROVIDER: scopus
PMCID: PMC6856724
Notes: Article -- Export Date: 2 December 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Kristian Helin
    29 Helin