Enzymes
UniProtKB help_outline | 4 proteins |
Reaction participants Show >> << Hide
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Namehelp_outline
cytidine34 in mitochondrial tRNA
Identifier
RHEA-COMP:13453
Reactive part
help_outline
- Name help_outline CMP residue Identifier CHEBI:82748 Charge -1 Formula C9H11N3O7P SMILEShelp_outline Nc1ccn([C@@H]2O[C@H](COP([O-])(-*)=O)[C@@H](O-*)[C@H]2O)c(=O)n1 2D coordinates Mol file for the small molecule Search links Involved in 66 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline S-adenosyl-L-methionine Identifier CHEBI:59789 Charge 1 Formula C15H23N6O5S InChIKeyhelp_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILEShelp_outline C[S+](CC[C@H]([NH3+])C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 868 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
5-methylcytidine34 in mitochondrial tRNA
Identifier
RHEA-COMP:13451
Reactive part
help_outline
- Name help_outline 5-methylcytidine 5'-phosphate residue Identifier CHEBI:74483 Charge -1 Formula C10H13N3O7P SMILEShelp_outline C1=C(C(=NC(N1[C@@H]2O[C@H](COP(*)(=O)[O-])[C@H]([C@H]2O)O*)=O)N)C 2D coordinates Mol file for the small molecule Search links Involved in 35 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline S-adenosyl-L-homocysteine Identifier CHEBI:57856 Charge 0 Formula C14H20N6O5S InChIKeyhelp_outline ZJUKTBDSGOFHSH-WFMPWKQPSA-N SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](CSCC[C@H]([NH3+])C([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 792 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:53076 | RHEA:53077 | RHEA:53078 | RHEA:53079 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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Related reactions help_outline
Specific form(s) of this reaction
More general form(s) of this reaction
Publications
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Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.
Van Haute L., Dietmann S., Kremer L., Hussain S., Pearce S.F., Powell C.A., Rorbach J., Lantaff R., Blanco S., Sauer S., Kotzaeridou U., Hoffmann G.F., Memari Y., Kolb-Kokocinski A., Durbin R., Mayr J.A., Frye M., Prokisch H., Minczuk M.
Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications ... >> More
Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m(5)C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNA(Met)). Further, we demonstrate that m(5)C deficiency in mt-tRNA(Met) results in the lack of 5-formylcytosine (f(5)C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f(5)C in human mitochondrial RNA is generated by oxidative processing of m(5)C. << Less
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NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met).
Nakano S., Suzuki T., Kawarada L., Iwata H., Asano K., Suzuki T.
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, ... >> More
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. << Less
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NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation.
Haag S., Sloan K.E., Ranjan N., Warda A.S., Kretschmer J., Blessing C., Huebner B., Seikowski J., Dennerlein S., Rehling P., Rodnina M.V., Hoebartner C., Bohnsack M.T.
Mitochondrial gene expression uses a non-universal genetic code in mammals. Besides reading the conventional AUG codon, mitochondrial (mt-)tRNA<sup>M</sup><sup>et</sup> mediates incorporation of methionine on AUA and AUU codons during translation initiation and on AUA codons during elongation. We ... >> More
Mitochondrial gene expression uses a non-universal genetic code in mammals. Besides reading the conventional AUG codon, mitochondrial (mt-)tRNA<sup>M</sup><sup>et</sup> mediates incorporation of methionine on AUA and AUU codons during translation initiation and on AUA codons during elongation. We show that the RNA methyltransferase NSUN3 localises to mitochondria and interacts with mt-tRNA<sup>M</sup><sup>et</sup> to methylate cytosine 34 (C34) at the wobble position. NSUN3 specifically recognises the anticodon stem loop (ASL) of the tRNA, explaining why a mutation that compromises ASL basepairing leads to disease. We further identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m<sup>5</sup>C34 of mt-tRNA<sup>M</sup><sup>et</sup> to generate an f<sup>5</sup>C34 modification. In vitro codon recognition studies with mitochondrial translation factors reveal preferential utilisation of m<sup>5</sup>C34 mt-tRNA<sup>Met</sup> in initiation. Depletion of either NSUN3 or ABH1 strongly affects mitochondrial translation in human cells, implying that modifications generated by both enzymes are necessary for mt-tRNA<sup>M</sup><sup>et</sup> function. Together, our data reveal how modifications in mt-tRNA<sup>M</sup><sup>et</sup> are generated by the sequential action of NSUN3 and ABH1, allowing the single mitochondrial tRNA<sup>M</sup><sup>et</sup> to recognise the different codons encoding methionine. << Less
EMBO J. 35:2104-2119(2016) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.