Scholler, Eva and Marks, James and Marchand, Virginie and Bruckmann, Astrid and Powell, Christopher A. and Reichold, Markus and Mutti, Christian Daniel and Dettmer, Katja and Feederle, Regina and Huttelmaier, Stefan and Helm, Mark and Oefner, Peter and Minczuk, Michal and Motorin, Yuri and Hafner, Markus and Meister, Gunter (2021) Balancing of mitochondrial translation through METTL8-mediated m(3)C modification of mitochondrial tRNAs. MOLECULAR CELL, 81 (23). 4810-+. ISSN 1097-2765, 1097-4164
Full text not available from this repository. (Request a copy)Abstract
Mitochondria contain a specific translation machinery for the synthesis of mitochondria-encoded respiratory chain components. Mitochondrial tRNAs (mt-tRNAs) are also generated from the mitochondrial DNA and, similar to their cytoplasmic counterparts, are post-transcriptionally modified. Here, we find that the RNA methyltransferase METTL8 is a mitochondrial protein that facilitates 3-methyl-cytidine (m(3)C) methylation at position C-32 of the mt-tRNA(ser(UCN)) and mt-tRNA(Thr). METTL8 knockout cells show a reduction in respiratory chain activity, whereas overexpression increases activity. In pancreatic cancer, METTL8 levels are high, which correlates with lower patient survival and an enhanced respiratory chain activity. Mitochondrial ribosome profiling uncovered mitoribosome stalling on mt-tRNA(ser(UCN)) - and mt-tRNA(Thr) -dependent codons. Further analysis of the respiratory chain complexes using mass spectrometry revealed reduced incorporation of the mitochondrially encoded proteins ND6 and ND1 into complex I. The well-balanced translation of mt-tRNA(ser(UCN)) - and mt-tRNA(Thr) -dependent codons through METTL8-mediated m(3)C(32) methylation might, therefore, facilitate the optimal composition and function of the mitochondria! respiratory chain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESSENGER-RNA; POSTTRANSCRIPTIONAL MODIFICATIONS; M(6)A METHYLTRANSFERASE; SEQUENCE; TRANSCRIPTION; METHYLATION; COMPLEX; METTL16; FATE; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Sep 2022 13:39 |
| Last Modified: | 06 Sep 2022 13:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46732 |
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