Contribution of a mitochondrial tyrosyl-tRNA synthetase mutation to the phenotypic expression of the deafness-associated tRNA^Ser(UCN) 7511A>G mutation.

ABSTRACT: Nuclear modifier genes have been proposed to modify the phenotypic expression of mitochondrial DNA mutations. Using a targeted exome-sequencing approach, here we found that the p.191Gly>Val mutation in mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) interacts with the tRNA^Ser(UCN) 7511A>G mutation in causing deafness. Strikingly, members of a Chinese family bearing both the YARS2 p.191Gly>Val and m.7511A>G mutations displayed much higher penetrance of deafness than those pedigrees carrying only the m.7511A>G mutation. The m.7511A>G mutation changed the A4:U69 base-pairing to G4:U69 pairing at the aminoacyl acceptor stem of tRNA^Ser(UCN) and perturbed tRNA^Ser(UCN) structure and function, including an increased melting temperature, altered conformation, instab

SUBMITTER: Fan W 

PROVIDER: S-EPMC6916496 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature