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

Author

Listed:
  • Sammy Villa

    (University of California
    1170 Veterans Boulevard)

  • Pankaj Dwivedi

    (1 DNA Way
    Merck)

  • Aaron Stahl

    (University of Iowa
    Scripps Research)

  • Trent Hinkle

    (1 DNA Way)

  • Christopher M. Rose

    (1 DNA Way)

  • Donald S. Kirkpatrick

    (1 DNA Way
    Xaira Therapeutics)

  • Seth M. Tomchik

    (University of Iowa
    Scripps Research
    University of Iowa
    University of Iowa)

  • Vishva M. Dixit

    (1 DNA Way)

  • Fred W. Wolf

    (University of California
    University of California)

Abstract

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.

Suggested Citation

  • Sammy Villa & Pankaj Dwivedi & Aaron Stahl & Trent Hinkle & Christopher M. Rose & Donald S. Kirkpatrick & Seth M. Tomchik & Vishva M. Dixit & Fred W. Wolf, 2024. "OTUD6 deubiquitination of RPS7/eS7 on the free 40 S ribosome regulates global protein translation and stress," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51284-y
    DOI: 10.1038/s41467-024-51284-y
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