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A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit

Author

Listed:
  • Pedro Rebelo-Guiomar

    (University of Cambridge, Cambridge Biomedical Campus)

  • Simone Pellegrino

    (University of Cambridge, Cambridge Biomedical Campus
    Cambridge Biomedical Campus, Jeffrey Cheah Biomedical Centre
    University of Cambridge, Cambridge Biomedical Campus, Jeffrey Cheah Biomedical Centre)

  • Kyle C. Dent

    (University of Cambridge, Cambridge Biomedical Campus
    Cambridge Biomedical Campus, Jeffrey Cheah Biomedical Centre
    University of Cambridge, Cambridge Biomedical Campus, Jeffrey Cheah Biomedical Centre
    Cambridge Biomedical Campus)

  • Aldema Sas-Chen

    (Weizmann Institute of Science
    Tel Aviv University)

  • Leonor Miller-Fleming

    (University of Cambridge, Cambridge Biomedical Campus)

  • Caterina Garone

    (University of Cambridge, Cambridge Biomedical Campus
    University of Bologna)

  • Lindsey Van Haute

    (University of Cambridge, Cambridge Biomedical Campus)

  • Jack F. Rogan

    (STORM Therapeutics Limited, Babraham Research Campus)

  • Adam Dinan

    (University of Cambridge)

  • Andrew E. Firth

    (University of Cambridge)

  • Byron Andrews

    (STORM Therapeutics Limited, Babraham Research Campus)

  • Alexander J. Whitworth

    (University of Cambridge, Cambridge Biomedical Campus)

  • Schraga Schwartz

    (Weizmann Institute of Science)

  • Alan J. Warren

    (University of Cambridge, Cambridge Biomedical Campus
    Cambridge Biomedical Campus, Jeffrey Cheah Biomedical Centre
    University of Cambridge, Cambridge Biomedical Campus, Jeffrey Cheah Biomedical Centre)

  • Michal Minczuk

    (University of Cambridge, Cambridge Biomedical Campus)

Abstract

Many cellular processes, including ribosome biogenesis, are regulated through post-transcriptional RNA modifications. Here, a genome-wide analysis of the human mitochondrial transcriptome shows that 2’-O-methylation is limited to residues of the mitoribosomal large subunit (mtLSU) 16S mt-rRNA, introduced by MRM1, MRM2 and MRM3, with the modifications installed by the latter two proteins being interdependent. MRM2 controls mitochondrial respiration by regulating mitoribosome biogenesis. In its absence, mtLSU particles (visualized by cryo-EM at the resolution of 2.6 Å) present disordered RNA domains, partial occupancy of bL36m and bound MALSU1:L0R8F8:mtACP anti-association module, allowing five mtLSU biogenesis intermediates with different intersubunit interface configurations to be placed along the assembly pathway. However, mitoribosome biogenesis does not depend on the methyltransferase activity of MRM2. Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. This work identifies a key checkpoint during mtLSU assembly, essential to maintain mitochondrial homeostasis.

Suggested Citation

  • Pedro Rebelo-Guiomar & Simone Pellegrino & Kyle C. Dent & Aldema Sas-Chen & Leonor Miller-Fleming & Caterina Garone & Lindsey Van Haute & Jack F. Rogan & Adam Dinan & Andrew E. Firth & Byron Andrews &, 2022. "A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28503-5
    DOI: 10.1038/s41467-022-28503-5
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    References listed on IDEAS

    as
    1. Katerina Naydenova & Christopher J. Russo, 2017. "Measuring the effects of particle orientation to improve the efficiency of electron cryomicroscopy," Nature Communications, Nature, vol. 8(1), pages 1-5, December.
    2. Miriam Cipullo & Genís Valentín Gesé & Anas Khawaja & B. Martin Hällberg & Joanna Rorbach, 2021. "Structural basis for late maturation steps of the human mitoribosomal large subunit," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    3. Jingdong Cheng & Otto Berninghausen & Roland Beckmann, 2021. "A distinct assembly pathway of the human 39S late pre-mitoribosome," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Hauke S. Hillen & Elena Lavdovskaia & Franziska Nadler & Elisa Hanitsch & Andreas Linden & Katherine E. Bohnsack & Henning Urlaub & Ricarda Richter-Dennerlein, 2021. "Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
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    Cited by:

    1. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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