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

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 Kirino, Rolf Wibom, Oliver Rackham, Aleksandra Filipovska, Joanna Rorbach, Christoph Freyer () and Anna Wredenberg ()
Additional contact information
Paula Clemente: Karolinska Institutet
Javier Calvo-Garrido: Karolinska Institutet
Sarah F. Pearce: Karolinska Institutet
Florian A. Schober: Karolinska Institutet
Megumi Shigematsu: Thomas Jefferson University
Stefan J. Siira: 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
Oliver Rackham: QEII Medical Centre and University of Western Australia
Aleksandra Filipovska: QEII Medical Centre and University of Western Australia
Joanna Rorbach: Karolinska Institutet
Christoph Freyer: Karolinska Institutet
Anna Wredenberg: Karolinska Institutet

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33368-9

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