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eIF6 rebinding dynamically couples ribosome maturation and translation

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  • Pekka Jaako

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    Sahlgrenska Center for Cancer Research, Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg)

  • Alexandre Faille

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus)

  • Shengjiang Tan

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus)

  • Chi C. Wong

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Cambridge University Hospitals)

  • Norberto Escudero-Urquijo

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus)

  • Pablo Castro-Hartmann

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus)

  • Penny Wright

    (Cambridge University Hospitals)

  • Christine Hilcenko

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus)

  • David J. Adams

    (Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus)

  • Alan J. Warren

    (Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building
    Wellcome Trust–Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus)

Abstract

Protein synthesis is a cyclical process consisting of translation initiation, elongation, termination and ribosome recycling. The release factors SBDS and EFL1—both mutated in the leukemia predisposition disorder Shwachman-Diamond syndrome — license entry of nascent 60S ribosomal subunits into active translation by evicting the anti-association factor eIF6 from the 60S intersubunit face. We find that in mammalian cells, eIF6 holds all free cytoplasmic 60S subunits in a translationally inactive state and that SBDS and EFL1 are the minimal components required to recycle these 60S subunits back into additional rounds of translation by evicting eIF6. Increasing the dose of eIF6 in mice in vivo impairs terminal erythropoiesis by sequestering post-termination 60S subunits in the cytoplasm, disrupting subunit joining and attenuating global protein synthesis. These data reveal that ribosome maturation and recycling are dynamically coupled by a mechanism that is disrupted in an inherited leukemia predisposition disorder.

Suggested Citation

  • Pekka Jaako & Alexandre Faille & Shengjiang Tan & Chi C. Wong & Norberto Escudero-Urquijo & Pablo Castro-Hartmann & Penny Wright & Christine Hilcenko & David J. Adams & Alan J. Warren, 2022. "eIF6 rebinding dynamically couples ribosome maturation and translation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29214-7
    DOI: 10.1038/s41467-022-29214-7
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    References listed on IDEAS

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    3. Shengjiang Tan & Laëtitia Kermasson & Christine Hilcenko & Vasileios Kargas & David Traynor & Ahmed Z. Boukerrou & Norberto Escudero-Urquijo & Alexandre Faille & Alexis Bertrand & Maxim Rossmann & Bea, 2021. "Somatic genetic rescue of a germline ribosome assembly defect," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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    Cited by:

    1. Antonios Apostolopoulos & Naohiro Kawamoto & Siu Yu A. Chow & Hitomi Tsuiji & Yoshiho Ikeuchi & Yuichi Shichino & Shintaro Iwasaki, 2024. "dCas13-mediated translational repression for accurate gene silencing in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Heather E. Machado & Nina F. Øbro & Nicholas Williams & Shengjiang Tan & Ahmed Z. Boukerrou & Megan Davies & Miriam Belmonte & Emily Mitchell & E. Joanna Baxter & Nicole Mende & Anna Clay & Philip Anc, 2023. "Convergent somatic evolution commences in utero in a germline ribosomopathy," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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