OTUD6 deubiquitination of RPS7/eS7 on the free 40 S ribosome regulates global protein translation and stress.

Autor: Villa S; Quantitative and Systems Biology, University of California, Merced, CA, 95343, USA.; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA, 94080, USA., Dwivedi P; Department of Microchemistry, Proteomics, and Lipidomics, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.; Merck, West Point, PA, 19486, USA., Stahl A; Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.; Department of Neuroscience, Scripps Research, Jupiter, FL, 33458, USA., Hinkle T; Department of Microchemistry, Proteomics, and Lipidomics, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA., Rose CM; Department of Microchemistry, Proteomics, and Lipidomics, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA., Kirkpatrick DS; Department of Microchemistry, Proteomics, and Lipidomics, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.; Xaira Therapeutics, Brisbane, CA, 94005, USA., Tomchik SM; Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.; Department of Neuroscience, Scripps Research, Jupiter, FL, 33458, USA.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA.; Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, 52242, USA., Dixit VM; Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA., Wolf FW; Quantitative and Systems Biology, University of California, Merced, CA, 95343, USA. fwolf@ucmerced.edu.; Department of Molecular and Cell Biology, University of California, Merced, CA, 95343, USA. fwolf@ucmerced.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 11; Vol. 15 (1), pp. 6873. Date of Electronic Publication: 2024 Aug 11.
DOI: 10.1038/s41467-024-51284-y
Abstrakt: Ribosomes are regulated by evolutionarily conserved ubiquitination/deubiquitination events. We uncover the role of the deubiquitinase OTUD6 in regulating global protein translation through deubiquitination of the RPS7/eS7 subunit on the free 40 S ribosome in vivo in Drosophila. Coimmunoprecipitation and enrichment of monoubiquitinated proteins from catalytically inactive OTUD6 flies reveal RPS7 as the ribosomal substrate. The 40 S protein RACK1 and E3 ligases CNOT4 and RNF10 function upstream of OTUD6 to regulate alkylation stress. OTUD6 interacts with RPS7 specifically on the free 40 S, and not on 43 S/48 S initiation complexes or the translating ribosome. Global protein translation levels are bidirectionally regulated by OTUD6 protein abundance. OTUD6 protein abundance is physiologically regulated in aging and in response to translational and alkylation stress. Thus, OTUD6 may promote translation initiation, the rate limiting step in protein translation, by titering the amount of 40 S ribosome that recycles.
(© 2024. The Author(s).)
Databáze: MEDLINE
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