A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C
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 ubi...
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Nature Publishing Group
2015
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| Online Access: | https://eprints.nottingham.ac.uk/37552/ |
| _version_ | 1848795482782957568 |
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| author | Cano, Florencia Rapiteanu, Radu Winkler, G.S. Lehner, Paul J. |
| author_facet | Cano, Florencia Rapiteanu, Radu Winkler, G.S. Lehner, Paul J. |
| author_sort | Cano, Florencia |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:32:48Z |
| format | Article |
| id | nottingham-37552 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:32:48Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-375522020-05-04T17:19:20Z https://eprints.nottingham.ac.uk/37552/ 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. 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. Nature Publishing Group 2015-10-16 Article PeerReviewed Cano, Florencia, Rapiteanu, Radu, Winkler, G.S. and Lehner, Paul J. (2015) A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C. Nature Communications, 6 . 8670/1-8670/8. ISSN 2041-1723 RNA decay Ubiquitin ligases Ubiquitins http://www.nature.com/articles/ncomms9670 doi:10.1038/ncomms9670 doi:10.1038/ncomms9670 |
| spellingShingle | RNA decay Ubiquitin ligases Ubiquitins Cano, Florencia Rapiteanu, Radu Winkler, G.S. Lehner, Paul J. A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C |
| title | A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C |
| title_full | A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C |
| title_fullStr | A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C |
| title_full_unstemmed | A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C |
| title_short | A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C |
| title_sort | non-proteolytic role for ubiquitin in deadenylation by the rna-binding e3 ligase mex-3c |
| topic | RNA decay Ubiquitin ligases Ubiquitins |
| url | https://eprints.nottingham.ac.uk/37552/ https://eprints.nottingham.ac.uk/37552/ https://eprints.nottingham.ac.uk/37552/ |