title: A non-proteolytic role for ubiquitin in deadenylation of MHC-I mRNA by the RNA-binding E3-ligase MEX-3C.
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.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.|Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Florencia
authors.initials: F
authors.lastname: Cano
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Radu
authors.initials: R
authors.lastname: Rapiteanu
authors.affiliation: School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: G
authors.initials: G
authors.lastname: Sebastiaan Winkler
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lehner
mesh_terms: D005095:Exoribonucleases; D057809:HEK293 Cells; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D015789:HLA-A2 Antigen; C515359:MEX3C protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C545829:CNOT7 protein, human; D005095:Exoribonucleases