Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNALys with the MERRF encephalomyopathy pathogenic mutation

[摘要]

A mitochondrial tRNA^Lys gene mutation at nucleotide position 8344 is responsible for the myoclonus epilepsy associated with ragged-red fibers (MERRF) subgroup of mitochondrial encephalomyopathies. Here, we show that normally modified uridine at the anticodon wobble position remains unmodified in the purified mutant tRNA^Lys. We have reported a similar modification defect at the same position in two mutant mitochondrial tRNAs^Leu(UUR) in another subgroup, mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), indicating this defect is common in the two kinds of tRNA molecules with the respective mutations of the two major mitochondrial encephalomyopathies. We therefore suggest the defect in the anticodon is responsible, through the translational process, for the pathogenesis of mitochondrial diseases.

[学科分类] 生物化学/生物物理

[关键词] Mitochondrial disease;Mitochondrial tRNA;Anticodon;Post-transcriptional modification;Cybrid;MERRF;myoclonus epilepsy associated with ragged-red fibers;np;nucleotide position;tRNALeu(UUR);leucine-specific tRNA corresponding to the codons UUR;where R means A or G;MELAS;mitochondrial myopathy;encephalopathy;lactic acidosis and stroke-like episodes;tRNALys(A8344G);MERRF patient-derived mitochondrial tRNALys harboring the A to G transition in TΨC-loop