• Medientyp: E-Artikel
  • Titel: RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation
  • Beteiligte: Poetz, Fabian [VerfasserIn]; Corbo, Joshua [VerfasserIn]; Levdansky, Yevgen [VerfasserIn]; Spiegelhalter, Alexander [VerfasserIn]; Lindner, Doris [VerfasserIn]; Magg, Vera [VerfasserIn]; Lebedeva, Svetlana [VerfasserIn]; Schweiggert, Jörg [VerfasserIn]; Schott, Johanna [VerfasserIn]; Valkov, Eugene [VerfasserIn]; Stoecklin, Georg [VerfasserIn]
  • Erschienen: 09 December 2021
  • Erschienen in: Nature Communications ; 12(2021), Artikel-ID 7175, Seite 1-19
  • Sprache: Englisch
  • DOI: 10.1038/s41467-021-27471-6
  • ISSN: 2041-1723
  • Identifikator:
  • Schlagwörter: RNA ; RNA decay
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: The CCR4-NOT complex acts as a central player in the control of mRNA turnover and mediates accelerated mRNA degradation upon HDAC inhibition. Here, we explored acetylation-induced changes in the composition of the CCR4-NOT complex by purification of the endogenously tagged scaffold subunit NOT1 and identified RNF219 as an acetylation-regulated cofactor. We demonstrate that RNF219 is an active RING-type E3 ligase which stably associates with CCR4-NOT via NOT9 through a short linear motif (SLiM) embedded within the C-terminal low-complexity region of RNF219. By using a reconstituted six-subunit human CCR4-NOT complex, we demonstrate that RNF219 inhibits deadenylation through the direct interaction of the α-helical SLiM with the NOT9 module. Transcriptome-wide mRNA half-life measurements reveal that RNF219 attenuates global mRNA turnover in cells, with differential requirement of its RING domain. Our results establish RNF219 as an inhibitor of CCR4-NOT-mediated deadenylation, whose loss upon HDAC inhibition contributes to accelerated mRNA turnover.
  • Zugangsstatus: Freier Zugang