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

Poetz, F.; Corbo, J.; Levdansky, Y.; Spiegelhalter, A.; Lindner, D.; Magg, V.; Lebedeva, S.; Schweiggert, J.; Schott, J.; Valkov, E.; Stoecklin, G.

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

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Item Type:	Article
Title:	RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation
Creators Name:	Poetz, F., Corbo, J., Levdansky, Y., Spiegelhalter, A., Lindner, D., Magg, V., Lebedeva, S., Schweiggert, J., Schott, J., Valkov, E. and Stoecklin, G.
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 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.
Keywords:	Adenosine Monophosphate, HeLa Cells, Protein Binding, RNA Stability, Messenger RNA, CCR4 Receptors, Transcription Factors, Ubiquitin-Protein Ligases, Ubiquitin-Protein Ligases / Metabolism
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	12
Number:	1
Page Range:	7175
Date:	9 December 2021
Official Publication:	https://doi.org/10.1038/s41467-021-27471-6
PubMed:	View item in PubMed

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