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

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  • Florencia Cano

    (Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute)

  • Radu Rapiteanu

    (Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus)

  • G. Sebastiaan Winkler

    (School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, University Park)

  • Paul J. Lehner

    (Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus)

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.

Suggested Citation

  • Florencia Cano & Radu Rapiteanu & G. Sebastiaan Winkler & Paul J. Lehner, 2015. "A non-proteolytic role for ubiquitin in deadenylation of MHC-I mRNA by the RNA-binding E3-ligase MEX-3C," Nature Communications, Nature, vol. 6(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9670
    DOI: 10.1038/ncomms9670
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    1. Ana Domingo-Muelas & Pere Duart-Abadia & Jose Manuel Morante-Redolat & Antonio Jordán-Pla & Germán Belenguer & Jaime Fabra-Beser & Lucía Paniagua-Herranz & Ana Pérez-Villalba & Adrián Álvarez-Varela &, 2023. "Post-transcriptional control of a stemness signature by RNA-binding protein MEX3A regulates murine adult neurogenesis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Fabian Poetz & Joshua Corbo & Yevgen Levdansky & Alexander Spiegelhalter & Doris Lindner & Vera Magg & Svetlana Lebedeva & Jörg Schweiggert & Johanna Schott & Eugene Valkov & Georg Stoecklin, 2021. "RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

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