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RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation

  1. Author:
    Poetz, Fabian
    Corbo,Joshua
    Levdansky,Yevgen
    Spiegelhalter, Alexander
    Lindner, Doris
    Magg, Vera
    Lebedeva, Svetlana
    Schweiggert, Jorg
    Schott, Johanna
    Valkov,Eugene
    Stoecklin, Georg

  2. Author Address

    Heidelberg Univ, Mannheim Inst Innate Immunosci MI3, Med Fac Mannheim, Div Biochem, D-68167 Mannheim, Germany.Heidelberg Univ ZMBH, German Canc Res Ctr DKFZ ZMBH Alliance, Ctr Mol Biol, D-69120 Heidelberg, Germany.NCI, RNA Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.Heidelberg Univ, Dept Infect Dis, Ctr Integrat Infect Dis Res CIID, Mol Virol, D-69120 Heidelberg, Germany.Max Delbruck Ctr Mol Med, Berlin Inst Mol Syst Biol BIMSB, D-10115 Berlin, Germany.
    1. Year: 2021
    2. Date: Dec 9
  2. Journal: Nature Communications
  3. Nature Portfolio
    1. 12
    2. 1
  5. Type of Article: Article
  6. Article Number: 7175
  7. ISSN: 2041-1723
  1. Abstract:

    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 alpha-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.

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External Sources

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  2. DOI: 10.1038/s41467-021-27471-6
  3. PMID: 34887419
  4. View record in Web of Science®
  5. WOS: 000728562700020

Library Notes

  1. Fiscal Year: FY2021-2022
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