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The RNA methyltransferase METTL8 installs m\(^3\)C\(_{32}\) in mitochondrial tRNAs\(^{Thr/Ser(UCN)}\) to optimise tRNA structure and mitochondrial translation
Please always quote using this URN: urn:nbn:de:bvb:20-opus-254592
- Modified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase responsible for installing m\(^3\)C\(_{32}\) in the human mitochondrial (mt-)tRNA\(^{Thr}\) and mt-tRNA\(^{Ser(UCN)}\). METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mttRNA recognition elements revealed U\(_{34}\)G\(_{35}\) andModified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase responsible for installing m\(^3\)C\(_{32}\) in the human mitochondrial (mt-)tRNA\(^{Thr}\) and mt-tRNA\(^{Ser(UCN)}\). METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mttRNA recognition elements revealed U\(_{34}\)G\(_{35}\) and t\(^6\)A\(_{37}\)/(ms\(^2\))i\(^6\)A\(_{37}\), present concomitantly only in the ASLs of the two substrate mt-tRNAs, as key determinants for METTL8-mediated methylation of C\(_{32}\). Several lines of evidence demonstrate the influence of U\(_{34}\), G\(_{35}\), and the m\(^3\)C\(_{32}\) and t\(^6\)A\(_{37}\)/(ms\(^2\))i\(^6\)A\(_{37}\) modifications in mt-tRNA\(^{Thr/Ser(UCN)}\) on the structure of these mt-tRNAs. Although mt-tRNA\(^{Thr/Ser(UCN)}\) lacking METTL8-mediated m\(^3\)C\(_{32}\) are efficiently aminoacylated and associate with mitochondrial ribosomes, mitochondrial translation is mildly impaired by lack of METTL8. Together these results define the cellular targets of METTL8 and shed new light on the role of m\(^3\)C\(_{32}\) within mt-tRNAs.…
Author: | Nicole KleiberORCiD, Nicolas Lemus-Diaz, Carina StillerORCiD, Marleen Heinrichs, Mandy Mong-Quyen Mai, Philipp Hackert, Ricarda Richter-DennerleinORCiD, Claudia HöbartnerORCiD, Katherine E. BohnsackORCiD, Markus T. BohnsackORCiD |
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URN: | urn:nbn:de:bvb:20-opus-254592 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Language: | English |
Parent Title (English): | Nature Communication |
Year of Completion: | 2022 |
Volume: | 13 |
Article Number: | 209 |
Source: | Nature Communications (2022) 13:209. https://doi.org/10.1038/s41467-021-27905-1 |
DOI: | https://doi.org/10.1038/s41467-021-27905-1 |
Sonstige beteiligte Institutionen: | Department of Molecular Biology, University Medical Centre Göttingen |
Sonstige beteiligte Institutionen: | Department of Cellular Biochemistry, University Medical Centre Göttingen |
Sonstige beteiligte Institutionen: | Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells, Göttingen |
Sonstige beteiligte Institutionen: | Göttingen Center for Molecular Biosciences, University of Göttingen |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Tag: | Enzymes; METTL8; Mitochondrial Matrix Protein; Modified Nucleotides in tRNAs; Organelles; RNA; RNA Methyltransferase |
Release Date: | 2022/02/03 |
EU-Project number / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |