A pathogenic point mutation reduces stability of mitochondrial mutant tRNAIle

AUTOR(ES)

Yasukawa, Takehiro

FONTE

Oxford University Press

RESUMO

Point mutations in mitochondrial tRNA genes are responsible for individual subgroups of mitochondrial encephalomyopathies. We have recently reported that point mutations in the tRNALeu(UUR) and tRNALys genes cause a defect in the normal modification at the first nucleotide of the anticodon. As part of a systematic analysis of pathogenic mutant mitochondrial tRNAs, we purified tRNAIle with a point mutation at nucleotide 4269 to determine its nucleotide sequence, including modified nucleotides. We found that, instead of causing a defect in the post-transcriptional modification, a pathogenic point mutation in the mitochondrial tRNAIle reduced the stability of the mutant tRNA molecule, resulting in a low steady-state level of aminoacyl-tRNA. The reduced stability was confirmed by examining the life-span of the mutant tRNAIle both in vitro and in vivo, as well as by monitoring its melting profile. Our finding indicates that the mutant tRNAIle itself is intrinsically unstable.

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