A Hypertension-Associated tRNAAla Mutation Alters tRNA Metabolism and Mitochondrial Function.

ABSTRACT: In this report, we investigated the pathophysiology of a novel hypertension-associated mitochondrial tRNA(Ala) 5655A → G (m.5655A → G) mutation. The destabilization of a highly conserved base pairing (A1-U72) at the aminoacyl acceptor stem by an m.5655A → G mutation altered the tRNA(Ala) function. An in vitro processing analysis showed that the m.5655A → G mutation reduced the efficiency of tRNA(Ala) precursor 5' end cleavage catalyzed by RNase P. By using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from a Chinese family into mitochondrial DNA (mtDNA)-less (ρ(o)) cells, we showed a 41% reduction in the steady-state level of tRNA(Ala) in mutant cybrids. The mutation caused an improperly aminoacylated tRNA(Ala), as suggested by aberrantly aminoacyl

SUBMITTER: Jiang P 

PROVIDER: S-EPMC4936059 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature