NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met)
| Autor: | Hiroyoshi Iwata, Kana Asano, Saori Nakano, Tsutomu Suzuki, Layla Kawarada, Takeo Suzuki |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetics Methionine Methyltransferase RNA Transfer Met RNA Mitochondrial RNA Cell Biology Methylation Cytidine Methyltransferases Mitochondrion Molecular biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Transfer RNA Protein biosynthesis Humans Molecular Biology Biogenesis |
| Zdroj: | Nature chemical biology. 12(7) |
| ISSN: | 1552-4469 |
| Popis: | In human mitochondria, the AUA codon encodes methionine via a mitochondrial transfer RNA for methionine (mt-tRNA(Met)) that contains 5-formylcytidine (f(5)C) at the first position of the anticodon (position 34). f(5)C34 is required for deciphering the AUA codon during protein synthesis. Until now, the biogenesis and physiological role of f(5)C34 were unknown. We demonstrate that biogenesis of f(5)C34 is initiated by S-adenosylmethionine (AdoMet)-dependent methylation catalyzed by NSUN3, a putative methyltransferase in mitochondria. NSUN3-knockout cells showed strong reduction in mitochondrial protein synthesis and reduced oxygen consumption, leading to deficient mitochondrial activity. We reconstituted formation of 5-methylcytidine (m(5)C) at position 34 (m(5)C34) on mt-tRNA(Met) with recombinant NSUN3 in the presence of AdoMet, demonstrating that NSUN3-mediated m(5)C34 formation initiates f(5)C34 biogenesis. We also found two disease-associated point mutations in mt-tRNA(Met) that impaired m(5)C34 formation by NSUN3, indicating that a lack of f(5)C34 has pathological consequences. |
| Databáze: | OpenAIRE |
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