MT-TM

MT-TM encodes mitochondrial tRNA-Met, one of the 22 transfer RNAs encoded by mitochondrial DNA. After excision from the polycistronic mtDNA transcript and post-transcriptional maturation, it is charged with methionine by the corresponding mitochondrial aminoacyl-tRNA synthetase and, in the mitochondrial matrix, acts as the adaptor that reads the methionine codons AUG and AUA (AUR) of the 13 mtDNA-encoded mRNAs on the mitoribosome, delivering methionine to the growing polypeptide. It is the single methionine tRNA of human mitochondria and serves both translation initiation and elongation. Reading of the AUA codon, which is methionine in the mitochondrial code, depends on 5-formylcytidine at wobble position 34, installed by NSUN3 and ALKBH1. Pathogenic variants in MT-TM, like those in other mt-tRNA genes, impair mitochondrial translation and oxidative phosphorylation and cause maternally inherited mitochondrial disease.