The RNA methyltransferase METTL8 installs m³C₃₂ in mitochondrial tRNAs^Thr/Ser(UCN) to optimise tRNA structure and mitochondrial translation.

ABSTRACT: Modified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase responsible for installing m³C₃₂ in the human mitochondrial (mt-)tRNA^Thr and mt-tRNA^Ser(UCN). METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mt-tRNA recognition elements revealed U₃₄G₃₅ and t⁶A₃₇/(ms²)i⁶A₃₇, present concomitantly only in the ASLs of the two substrate mt-tRNAs, as key determinants for METTL8-mediated methylation of C₃₂. Several lines of evidence dem

SUBMITTER: Kleiber N 

PROVIDER: S-EPMC8752778 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature