RNA modifications are critical in mediating how RNAs perform biological functions. Despite being less common, 3-methylcytidine (m3C) is discovered to be widely present in tRNAs, rRNAs, and mRNAs. A m3C methyltransferases for tRNAs, including transfer, is human METTL6 (UGA). In the presence of S-adenosyl-L-methionine, we were able to solve the structure of human METTL6, and an enzyme assay revealed that recombinant human METTL6 is active towards transfer (UGA). A putative tRNA binding area on the surface of METTL6 was identified by structural analysis, which also revealed the specific interactions between S-adenosyl-L-methionine and METTL6. In the near future, the design of effective METTL6 inhibitors will undoubtedly become clearer as a result of structural study that is accompanied by biochemical enzyme testing
