Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA^His mutation.

ABSTRACT: The deafness-associated m.12201T>C mutation affects the A5-U68 base-pairing within the acceptor stem of mitochondrial tRNA^His The primary defect in this mutation is an alteration in tRNA^His aminoacylation. Here, we further investigate the molecular mechanism of the deafness-associated tRNA^His 12201T>C mutation and test whether the overexpression of the human mitochondrial histidyl-tRNA synthetase gene (HARS2) in cytoplasmic hybrid (cybrid) cells carrying the m.12201T>C mutation reverses mitochondrial dysfunctions. Using molecular dynamics simulations, we demonstrate that the m.12201T>C mutation perturbs the tRNA^His structure and function, supported by decreased melting temperature, conformational changes, and instability of mutated tRNA. W

SUBMITTER: Gong S 

PROVIDER: S-EPMC6983842 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature