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Mechanism of mitoribosomal small subunit biogenesis and preinitiation

Author

Listed:
  • Yuzuru Itoh

    (Stockholm University)

  • Anas Khawaja

    (Karolinska Institute
    Max Planck Institute for Biology of Ageing-Karolinska Institutet Laboratory, Karolinska Institutet)

  • Ivan Laptev

    (Center of Life Sciences, Skolkovo Institute of Science and Technology
    Lomonosov Moscow State University
    Lomonosov Moscow State University)

  • Miriam Cipullo

    (Karolinska Institute
    Max Planck Institute for Biology of Ageing-Karolinska Institutet Laboratory, Karolinska Institutet)

  • Ilian Atanassov

    (Proteomics Core Facility, Max-Planck-Institute for Biology of Ageing)

  • Petr Sergiev

    (Center of Life Sciences, Skolkovo Institute of Science and Technology
    Lomonosov Moscow State University
    Lomonosov Moscow State University
    Lomonosov Moscow State University)

  • Joanna Rorbach

    (Karolinska Institute
    Max Planck Institute for Biology of Ageing-Karolinska Institutet Laboratory, Karolinska Institutet)

  • Alexey Amunts

    (Stockholm University)

Abstract

Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.

Suggested Citation

  • Yuzuru Itoh & Anas Khawaja & Ivan Laptev & Miriam Cipullo & Ilian Atanassov & Petr Sergiev & Joanna Rorbach & Alexey Amunts, 2022. "Mechanism of mitoribosomal small subunit biogenesis and preinitiation," Nature, Nature, vol. 606(7914), pages 603-608, June.
    • Handle: RePEc:nat:nature:v:606:y:2022:i:7914:d:10.1038_s41586-022-04795-x
    DOI: 10.1038/s41586-022-04795-x
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