Helmholtz Gemeinschaft


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

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Information)

Item Type:Article
Title:RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation
Creators Name:Poetz, F. and Corbo, J. and Levdansky, Y. and Spiegelhalter, A. and Lindner, D. and Magg, V. and Lebedeva, S. and Schweiggert, J. and Schott, J. and 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
Publisher:Nature Publishing Group
Page Range:7175
Date:9 December 2021
Official Publication:https://doi.org/10.1038/s41467-021-27471-6
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library