Deubiquitinase OTUD1 Resolves Stalled Translation on polyA and Rare Codon Rich mRNAs

OTUD1 is a deubiquitinating enzyme involved in many cellular processes including cancer and innate, immune signaling pathways. Here, we perform a proximity labeling-based interactome study that identifies OTUD1 largely present in the translation and RNA metabolism protein complexes. Biochemical anal...

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Bibliographic Details
Published in:Molecular and cellular biology 2022-12, Vol.42 (12), p.e0026522-e0026522
Main Authors: Snaurova, Renata, Vdovin, Alexander, Durech, Michal, Nezval, Jakub, Zihala, David, Jelinek, Tomas, Hajek, Roman, Simicek, Michal
Format: Article
Language:English
Subjects:
Carrier Proteins - metabolism
Codon
Deubiquitinating Enzymes - genetics
Deubiquitinating Enzymes - metabolism
Molecular and Cellular Biology
Poly A - metabolism
Protein Biosynthesis
Research Article
ribosome stalling
RNA, Messenger - genetics
RNA, Messenger - metabolism
translation
Ubiquitination
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Summary:OTUD1 is a deubiquitinating enzyme involved in many cellular processes including cancer and innate, immune signaling pathways. Here, we perform a proximity labeling-based interactome study that identifies OTUD1 largely present in the translation and RNA metabolism protein complexes. Biochemical analysis validates OTUD1 association with ribosome subunits, elongation factors and the E3 ubiquitin ligase ZNF598 but not with the translation initiation machinery. OTUD1 catalytic activity suppresses polyA triggered ribosome stalling through inhibition of ZNF598-mediated RPS10 ubiquitination and stimulates formation of polysomes. Finally, analysis of gene expression suggests that OTUD1 regulates the stability of rare codon rich mRNAs by antagonizing ZNF598.
ISSN:0270-7306
1098-5549
1098-5549
DOI:10.1128/mcb.00265-22