A pathogenic point mutation reduces stability of mitochondrial mutant tRNAIle
Open Access
- 1 October 2000
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 28 (19) , 3779-3784
- https://doi.org/10.1093/nar/28.19.3779
Abstract
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.Keywords
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