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Schöller, E.* ; Marks, J.* ; Marchand, V.* ; Bruckmann, A.* ; Powell, C.A.* ; Reichold, M.* ; Mutti, C.D.* ; Dettmer, K.* ; Feederle, R. ; Hüttelmaier, S.* ; Helm, M.* ; Oefner, P.* ; Minczuk, M.* ; Motorin, Y.* ; Hafner, M.* ; Meister, G.*

Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs.

Mol. Cell 81, 4810-4825.e12 (2021)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 (m3C) methylation at position C32 of the mt-tRNASer(UCN) and mt-tRNAThr. 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-tRNASer(UCN)- and mt-tRNAThr-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-tRNASer(UCN)- and mt-tRNAThr-dependent codons through METTL8-mediated m3C32 methylation might, therefore, facilitate the optimal composition and function of the mitochondrial respiratory chain.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mettl8 ; Rna Modification ; M(3)c ; Mt-trna ; Translation; Messenger-rna; Posttranscriptional Modifications; M(6)a Methyltransferase; Sequence; Transcription; Methylation; Complex; Mettl16; Fate
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Zeitschrift Molecular Cell
Quellenangaben Band: 81, Heft: 23, Seiten: 4810-4825.e12 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Förderungen Medical Research Council
European Research Council (ERC)
Grand Est Region (France) FRCR grant EpiARN
Bavarian Systems-Biology Network (Bio-SysNet)
Deutsche Forschungsgemeinschaft (DFG)