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Nucleic Acids Research, 2000, Vol. 28, No. 19 3779-3784
© 2000 Oxford University Press

A pathogenic point mutation reduces stability of mitochondrial mutant tRNAIle

Takehiro Yasukawa1,2, Narumi Hino3, Tsutomu Suzuki1,3, Kimitsuna Watanabe1,3, Takuya Ueda3 and Shigeo Ohta2,*

1Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, 2Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan and 3Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan

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.

* To whom correspondence should be addressed. Tel: +81 44 733 9267; Fax: +81 44 733 1877; Email: ohta@nms.ac.jp


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