Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs.

ABSTRACT: A subset of eukaryotic tRNAs is methylated in the anticodon loop, forming 3-methylcytosine (m³C) modifications. In mammals, the number of tRNAs containing m³C modifications has been expanded to include mitochondrial (mt) tRNA-Ser-UGA and mt-tRNA-Thr-UGU. However, whereas the enzymes catalyzing m³C formation in nuclear-encoded tRNAs have been identified, the proteins responsible for m³C modification in mt-tRNAs are unknown. Here, we show that m³C formation in human mt-tRNAs is dependent upon the methyltransferase-Like 8 (METTL8) enzyme. We find that METTL8 is a mitochondria-associated protein that interacts with mitochondrial seryl-tRNA synthetase, as well as with mt-tRNAs containing m³C. We demonstrate that human cells defic

SUBMITTER: Lentini JM 

PROVIDER: S-EPMC8980813 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature