Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression Journal Article

   


Authors: Garland, W.; Müller, I.; Wu, M.; Schmid, M.; Imamura, K.; Rib, L.; Sandelin, A.; Helin, K.; Jensen, T. H.
Article Title: Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression
Abstract: Transposable elements (TEs) are widespread genetic parasites known to be kept under tight transcriptional control. Here, we describe a functional connection between the mouse-orthologous “nuclear exosome targeting” (NEXT) and “human silencing hub” (HUSH) complexes, involved in nuclear RNA decay and the epigenetic silencing of TEs, respectively. Knocking out the NEXT component ZCCHC8 in embryonic stem cells results in elevated TE RNA levels. We identify a physical interaction between ZCCHC8 and the MPP8 protein of HUSH and establish that HUSH recruits NEXT to chromatin at MPP8-bound TE loci. However, while NEXT and HUSH both dampen TE RNA expression, their activities predominantly affect shorter non-polyadenylated and full-length polyadenylated transcripts, respectively. Indeed, our data suggest that the repressive action of HUSH promotes a condition favoring NEXT RNA decay activity. In this way, transcriptional and post-transcriptional machineries synergize to suppress the genotoxic potential of TE RNAs. © 2022 The Authors
Keywords: genetics; mouse; animal; metabolism; animals; mice; nuclear protein; nuclear proteins; rna; chromatin; rna stability; transposon; exosome; exosomes; dna transposable elements; transposable elements; exosome multienzyme ribonuclease complex; rna decay; rna exosome; retrotransposons; next complex; hush complex
Journal Title: Molecular Cell
Volume: 82
Issue: 9
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2022-05-05
Start Page: 1691
End Page: 1707
Language: English
DOI: 10.1016/j.molcel.2022.03.004
PUBMED: 35349793
PROVIDER: scopus
PMCID: PMC9433625
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85129247825&doi=10.1016%2fj.molcel.2022.03.004&partnerID=40&md5=7ef65fb43f1bc70e7628cd2c6342ab09
Notes: Article -- Export Date: 1 June 2022 -- Source: Scopus
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MSK Authors
  1. Kristian Helin
    33 Helin
  2. Iris Muller
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