Synthesis and properties of the anticodon stem-loop of human mitochondrial tRNAMet containing the disease-related G or m1G nucleosides at position 37

Abstract

A single point mutation (A4435G) in the human mitochondrial tRNA^Met (hmt-tRNA^Met) gene causes severe mitochondrial disorders associated with hypertension, type 2 diabetes and LHON. This mutation leads to the exchange of A₃₇ in the anticodon loop of hmt-tRNA^Met for G₃₇ and 1-methylguanosine (m¹G₃₇). Here we present the first synthesis and structural/biophysical studies of the anticodon stem and loop of pathogenic hmt-tRNAs^Met.