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Human mitochondria require mtRF1 for translation termination at non-canonical stop codons

Author

Listed:
  • Annika Krüger

    (Karolinska Institutet, Biomedicum
    Karolinska Institutet)

  • Cristina Remes

    (University of Pennsylvania)

  • Dmitrii Igorevich Shiriaev

    (Karolinska Institutet, Biomedicum
    Karolinska Institutet)

  • Yong Liu

    (Karolinska Institutet, Biomedicum
    Karolinska Institutet)

  • Henrik Spåhr

    (Karolinska Institutet, Biomedicum
    Karolinska Institutet)

  • Rolf Wibom

    (Karolinska Institutet)

  • Ilian Atanassov

    (Max-Planck-Institute for Biology of Ageing)

  • Minh Duc Nguyen

    (Karolinska Institutet, Biomedicum
    Karolinska Institutet)

  • Barry S. Cooperman

    (University of Pennsylvania)

  • Joanna Rorbach

    (Karolinska Institutet, Biomedicum
    Karolinska Institutet
    S.T.I.A.S: Stellenbosch Institute for Advanced Study)

Abstract

The mitochondrial translation machinery highly diverged from its bacterial counterpart. This includes deviation from the universal genetic code, with AGA and AGG codons lacking cognate tRNAs in human mitochondria. The locations of these codons at the end of COX1 and ND6 open reading frames, respectively, suggest they might function as stop codons. However, while the canonical stop codons UAA and UAG are known to be recognized by mtRF1a, the release mechanism at AGA and AGG codons remains a debated issue. Here, we show that upon the loss of another member of the mitochondrial release factor family, mtRF1, mitoribosomes accumulate specifically at AGA and AGG codons. Stalling of mitoribosomes alters COX1 transcript and protein levels, but not ND6 synthesis. In addition, using an in vitro reconstituted mitochondrial translation system, we demonstrate the specific peptide release activity of mtRF1 at the AGA and AGG codons. Together, our results reveal the role of mtRF1 in translation termination at non-canonical stop codons in mitochondria.

Suggested Citation

  • Annika Krüger & Cristina Remes & Dmitrii Igorevich Shiriaev & Yong Liu & Henrik Spåhr & Rolf Wibom & Ilian Atanassov & Minh Duc Nguyen & Barry S. Cooperman & Joanna Rorbach, 2023. "Human mitochondria require mtRF1 for translation termination at non-canonical stop codons," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35684-6
    DOI: 10.1038/s41467-022-35684-6
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    References listed on IDEAS

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    1. Takeo Suzuki & Yuka Yashiro & Ittoku Kikuchi & Yuma Ishigami & Hironori Saito & Ikuya Matsuzawa & Shunpei Okada & Mari Mito & Shintaro Iwasaki & Ding Ma & Xuewei Zhao & Kana Asano & Huan Lin & Yohei K, 2020. "Complete chemical structures of human mitochondrial tRNAs," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. Kazuki Saito & Hanna Kratzat & Annabelle Campbell & Robert Buschauer & A. Maxwell Burroughs & Otto Berninghausen & L. Aravind & Rachel Green & Roland Beckmann & Allen R. Buskirk, 2022. "Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria," Nature, Nature, vol. 603(7901), pages 503-508, March.
    3. Anas Khawaja & Yuzuru Itoh & Cristina Remes & Henrik Spåhr & Olessya Yukhnovets & Henning Höfig & Alexey Amunts & Joanna Rorbach, 2020. "Distinct pre-initiation steps in human mitochondrial translation," Nature Communications, Nature, vol. 11(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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