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ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing

Author

Listed:
  • Paula Clemente

    (Karolinska Institutet)

  • Javier Calvo-Garrido

    (Karolinska Institutet)

  • Sarah F. Pearce

    (Karolinska Institutet
    University of Edinburgh)

  • Florian A. Schober

    (Karolinska Institutet
    Max Planck Institute of Biochemistry)

  • Megumi Shigematsu

    (Thomas Jefferson University)

  • Stefan J. Siira

    (QEII Medical Centre and University of Western Australia
    QEII Medical Centre and University of Western Australia)

  • Isabelle Laine

    (Karolinska Institutet)

  • Henrik Spåhr

    (Karolinska Institutet)

  • Christian Steinmetzger

    (Karolinska Institutet)

  • Katja Petzold

    (Karolinska Institutet)

  • Yohei Kirino

    (Thomas Jefferson University)

  • Rolf Wibom

    (Karolinska Institutet
    Karolinska University Hospital)

  • Oliver Rackham

    (QEII Medical Centre and University of Western Australia
    QEII Medical Centre and University of Western Australia
    Curtin University
    Telethon Kids Institute, Northern Entrance, Perth Children’s Hospital)

  • Aleksandra Filipovska

    (QEII Medical Centre and University of Western Australia
    QEII Medical Centre and University of Western Australia
    Curtin University)

  • Joanna Rorbach

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

  • Christoph Freyer

    (Karolinska Institutet
    Karolinska University Hospital)

  • Anna Wredenberg

    (Karolinska Institutet
    Karolinska University Hospital)

Abstract

Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3′ phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis. Furthermore, our data suggest that members of the FAST kinase domain-containing protein family are responsible for these 3′ phosphates. Our results therefore propose a mechanism for non-canonical RNA processing in metazoan mitochondria, by identifying the role of ANGEL2.

Suggested Citation

  • Paula Clemente & Javier Calvo-Garrido & Sarah F. Pearce & Florian A. Schober & Megumi Shigematsu & Stefan J. Siira & Isabelle Laine & Henrik Spåhr & Christian Steinmetzger & Katja Petzold & Yohei Kiri, 2022. "ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33368-9
    DOI: 10.1038/s41467-022-33368-9
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    References listed on IDEAS

    as
    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.
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