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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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