RNA modification landscape of the human mitochondrial tRNA^Lys regulates protein synthesis.

ABSTRACT: Post-transcriptional RNA modifications play a critical role in the pathogenesis of human mitochondrial disorders, but the mechanisms by which specific modifications affect mitochondrial protein synthesis remain poorly understood. Here we used a quantitative RNA sequencing approach to investigate, at nucleotide resolution, the stoichiometry and methyl modifications of the entire mitochondrial tRNA pool, and establish the relevance to human disease. We discovered that a N¹-methyladenosine (m¹A) modification is missing at position 58 in the mitochondrial tRNA^Lys of patients with the mitochondrial DNA mutation m.8344 A > G associated with MERRF (myoclonus epilepsy, ragged-red fibers). By restoring the modification on the mitochondrial tRNA^Lys, we dem

SUBMITTER: Richter U 

PROVIDER: S-EPMC6160436 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature