Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs

Abstract

In human mitochondria, 1-methyladenosine (m¹A) occurs at position 58 of tRNA^Leu(UUR). In addition, partial m¹A58 modifications have been found in human mitochondrial tRNA^Lys and tRNA^Ser(UCN). We identified human Trmt61B, which encodes a mitochondria-specific tRNA methyltransferase responsible for m¹A58 in these three tRNAs. Trmt61B is dominantly localized to the mitochondria. m¹A58 formation in human mitochondrial tRNA^Leu(UUR) could be reconstituted in vitro using recombinant Trmt61B in the presence of Ado-Met as a methyl donor. Unlike the cytoplasmic tRNA m¹A58 methyltransferase that consists of an α2β2 heterotetramer formed by Trmt61A and Trmt6, Trmt61B formed a homo-oligomer (presumably a homotetramer) that resembled the bacterial homotetrameric m¹A58 methyltransferase. The bacterial origin of Trmt61B is supported by the results of the phylogenetic analysis.