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A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C

Cano, Florencia; Rapiteanu, Radu; Winkler, G.S.; Lehner, Paul J.

Authors

Florencia Cano florencia.cano@crick.ac.uk

Radu Rapiteanu

Paul J. Lehner pjl30@cam.ac.uk



Abstract

The regulation of protein and mRNA turnover is essential for many cellular processes. We recently showed that ubiquitin—traditionally linked to protein degradation—directly regulates the degradation of mRNAs through the action of a newly identified family of RNA-binding E3 ubiquitin ligases. How ubiquitin regulates mRNA decay remains unclear. Here, we identify a new role for ubiquitin in regulating deadenylation, the initial and often rate-limiting step in mRNA degradation. MEX-3C, a canonical member of this family of RNA-binding ubiquitin ligases, associates with the cytoplasmic deadenylation complexes and ubiquitinates CNOT7(Caf1), the main catalytic subunit of the CCR4-NOT deadenylation machinery. We establish a new role for ubiquitin in regulating MHC-I mRNA deadenylation as ubiquitination of CNOT7 by MEX-3C regulates its deadenylation activity and is required for MHC-I mRNA degradation. Since neither proteasome nor lysosome inhibitors rescued MEX-3C-mediated MHC-I mRNA degradation, our findings suggest a new non-proteolytic function for ubiquitin in the regulation of mRNA decay.

Journal Article Type Article
Publication Date Oct 16, 2015
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 6
Article Number 8670
APA6 Citation Cano, F., Rapiteanu, R., Winkler, G., & Lehner, P. J. (2015). A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C. Nature Communications, 6, https://doi.org/10.1038/ncomms9670
DOI https://doi.org/10.1038/ncomms9670
Keywords RNA decay, Ubiquitin ligases, Ubiquitins
Publisher URL http://www.nature.com/articles/ncomms9670
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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