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

Renata Snaurova1,2,3, Alexander Vdovin1,2,3, Michal Durech1,2

  • 1Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.

Molecular and Cellular Biology
|November 29, 2022
PubMed

Insights

The deubiquitinase OTUD1 interacts with translation machinery, preventing ribosome stalling and promoting mRNA stability. It inhibits ZNF598 to regulate protein synthesis and RNA metabolism in cells.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • OTUD1 (deubiquitinating enzyme) plays roles in cancer and immune signaling.
  • Its precise function in cellular processes remains incompletely understood.

Purpose of the Study:

  • To investigate the protein interactions and cellular functions of OTUD1.
  • To elucidate OTUD1's role in translation and RNA metabolism.

Main Methods:

  • Proximity labeling-based interactome study.
  • Biochemical assays to validate protein associations.
  • Analysis of gene expression and mRNA stability.

Main Results:

  • OTUD1 was identified in translation and RNA metabolism complexes, associating with ribosome subunits and elongation factors.
  • OTUD1 suppresses polyA-triggered ribosome stalling by inhibiting ZNF598-mediated RPS10 ubiquitination.
  • OTUD1 promotes polysome formation and regulates the stability of rare codon-rich mRNAs by antagonizing ZNF598.

Conclusions:

  • OTUD1 is a key regulator of translation and mRNA stability.
  • OTUD1's deubiquitinating activity impacts ribosome function and gene expression through ZNF598 antagonism.
Keywords:
ribosome stallingtranslationubiquitination

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