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An E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes.
Oltion, Keely; Carelli, Jordan D; Yang, Tangpo; See, Stephanie K; Wang, Hao-Yuan; Kampmann, Martin; Taunton, Jack.
Afiliação
  • Oltion K; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Carelli JD; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Yang T; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • See SK; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Wang HY; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kampmann M; Institute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Taunton J; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: jack.taunton@ucsf.edu.
Cell ; 186(2): 346-362.e17, 2023 01 19.
Article em En | MEDLINE | ID: mdl-36638793
Ribosomes frequently stall during mRNA translation, resulting in the context-dependent activation of quality control pathways to maintain proteostasis. However, surveillance mechanisms that specifically respond to stalled ribosomes with an occluded A site have not been identified. We discovered that the elongation factor-1α (eEF1A) inhibitor, ternatin-4, triggers the ubiquitination and degradation of eEF1A on stalled ribosomes. Using a chemical genetic approach, we unveiled a signaling network comprising two E3 ligases, RNF14 and RNF25, which are required for eEF1A degradation. Quantitative proteomics revealed the RNF14 and RNF25-dependent ubiquitination of eEF1A and a discrete set of ribosomal proteins. The ribosome collision sensor GCN1 plays an essential role by engaging RNF14, which directly ubiquitinates eEF1A. The site-specific, RNF25-dependent ubiquitination of the ribosomal protein RPS27A/eS31 provides a second essential signaling input. Our findings illuminate a ubiquitin signaling network that monitors the ribosomal A site and promotes the degradation of stalled translation factors, including eEF1A and the termination factor eRF1.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transativadores / Proteínas de Ligação a RNA Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transativadores / Proteínas de Ligação a RNA Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos