Enzymes
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Reaction participants Show >> << Hide
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Namehelp_outline
a cytidine in tRNA
Identifier
RHEA-COMP:13670
Reactive part
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- 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 904 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
an N3-methylcytidine in tRNA
Identifier
RHEA-COMP:15709
Reactive part
help_outline
- Name help_outline N3-methylcytidine 5'-phosphate residue Identifier CHEBI:74894 Charge -1 Formula C10H13N3O7P SMILEShelp_outline C1=CC(N(C(N1[C@@H]2O[C@H](COP(*)(=O)[O-])[C@H]([C@H]2O)O*)=O)C)=N 2D coordinates Mol file for the small molecule Search links Involved in 7 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 827 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 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:60908 | RHEA:60909 | RHEA:60910 | RHEA:60911 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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| Gene Ontology help_outline |
Related reactions help_outline
Specific form(s) of this reaction
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Publications
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Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and mRNA in mice and humans.
Xu L., Liu X., Sheng N., Oo K.S., Liang J., Chionh Y.H., Xu J., Ye F., Gao Y.G., Dedon P.C., Fu X.Y.
Chemical RNA modifications are central features of epitranscriptomics, highlighted by the discovery of modified ribonucleosides in mRNA and exemplified by the critical roles of RNA modifications in normal physiology and disease. Despite a resurgent interest in these modifications, the biochemistry ... >> More
Chemical RNA modifications are central features of epitranscriptomics, highlighted by the discovery of modified ribonucleosides in mRNA and exemplified by the critical roles of RNA modifications in normal physiology and disease. Despite a resurgent interest in these modifications, the biochemistry of 3-methylcytidine (m<sup>3</sup>C) formation in mammalian RNAs is still poorly understood. However, the recent discovery of <i>trm141</i> as the second gene responsible for m<sup>3</sup>C presence in RNA in fission yeast raises the possibility that multiple enzymes are involved in m<sup>3</sup>C formation in mammals as well. Here, we report the discovery and characterization of three distinct m<sup>3</sup>C-contributing enzymes in mice and humans. We found that methyltransferase-like (METTL) 2 and 6 contribute m<sup>3</sup>C in specific tRNAs and that METTL8 only contributes m<sup>3</sup>C to mRNA. MS analysis revealed that there is an ∼30-40% and ∼10-15% reduction, respectively, in <i>METTL2</i> and <i>-6</i> null-mutant cells, of m<sup>3</sup>C in total tRNA, and primer extension analysis located METTL2-modified m<sup>3</sup>C at position 32 of tRNA<sup>Thr</sup> isoacceptors and tRNA<sup>Arg(CCU)</sup> We also noted that METTL6 interacts with seryl-tRNA synthetase in an RNA-dependent manner, suggesting a role for METTL6 in modifying serine tRNA isoacceptors. <i>METTL8</i>, however, modified only mRNA, as determined by biochemical and genetic analyses in <i>Mettl8</i> null-mutant mice and two human <i>METTL8</i> mutant cell lines. Our findings provide the first evidence of the existence of m<sup>3</sup>C modification in mRNA, and the discovery of METTL8 as an mRNA m<sup>3</sup>C writer enzyme opens the door to future studies of other m<sup>3</sup>C epitranscriptomic reader and eraser functions. << Less
J. Biol. Chem. 292:14695-14703(2017) [PubMed] [EuropePMC]
This publication is cited by 4 other entries.