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

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...

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Hauptverfasser: 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)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 09 December 2021
In: Nature Communications
Year: 2021, Jahrgang: 12, Pages: 1-19
ISSN:2041-1723
DOI:10.1038/s41467-021-27471-6
Online-Zugang:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1038/s41467-021-27471-6
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-021-27471-6
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Verfasserangaben:Fabian Poetz, Joshua Corbo, Yevgen Levdansky, Alexander Spiegelhalter, Doris Lindner, Vera Magg, Svetlana Lebedeva, Jörg Schweiggert, Johanna Schott, Eugene Valkov & Georg Stoecklin
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Zusammenfassung: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.
Beschreibung:Gesehen am 27.09.2022
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-021-27471-6

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