A hypertension-associated mitochondrial DNA mutation introduces an m¹G37 modification into tRNA^Met, altering its structure and function.

ABSTRACT: Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A→G mutation in mitochondrial tRNA^Met The m.4435A→G mutation affected a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m.4435A→G mutation introduced an m¹G37 modification of tRNA^Met, altering its structure and function. Primer extension and methylation activity assays indeed confirmed that the m.4435A→G mutation created a tRNA methyltransferase 5 (TRMT5)-catalyz

SUBMITTER: Zhou M 

PROVIDER: S-EPMC5787817 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature