Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27471-6
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [273941853-SPP 1935, 278001972-TRR 186, 439669440-TRR 319]
- Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Ask authors/readers for more resources
The study identified RNF219 as an acetylation-regulated cofactor of the CCR4-NOT complex, which inhibits mRNA degradation mediated by the complex through interaction with NOT9. RNF219 attenuates global mRNA turnover in cells with a differential requirement of its RING domain.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available