Wobble modification defect in tRNA disturbs codon-anticodon interaction in a mitochondrial disease

• Yasukawa Takehiro

  Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School

• Suzuki Tsutomu

  Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo

• Ishii Norie

  Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School

• Ohta Shigeo

  Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School

• Watanabe Kimitsuna

  Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo Corresponding author

抄録

We previously showed that in mitochondrial tRNA^<Lys> with an A8344G mutation responsible for myoclonus epilepsy associated with ragged-red fibers (MERRF), a subgroup of mitochondrial encephalomyopathic diseases, the normally modified wobble base (a 2-thio-uridine derivative) remains unmodified. Since wobble base modifications are essential for translational efficiency and accuracy, we used mitochondrial components to estimate the translational activity in vitro of purified tRNA^<Lys> carrying the mutation and found no mistranslation of non-cognate codons by the mutant tRNA, but almost complete loss of translational activity for cognate codons. This defective translation was not explained by a decline in amino-acylation or lowered affinity toward elongation factor Tu. However, when direct interaction of the codon with the mutant tRNA^<Lys> defective anticodon was examined by ribosomal binding analysis, the wild-type but not the mutant tRNA^<Lys> bound to an mRNA-ribosome complex. We therefore concluded that the anticodon base modification defect, which is forced by the pathogenic point mutation, disturbs codon-anticodon pairing in the mutant tRNA^<Lys>, leading to a severe reduction in mitochondrial translation that eventually could result in the onset of MERRF.

収録刊行物

• 日本医科大学老人病研究所紀要

  日本医科大学老人病研究所紀要 8 35-43, 2002-03-25

  日本医科大学

キーワード

• anticodon
• mitochondrial disease
• mitochondrial translation
• mitochondrial tRNA
• post-transcriptional modification

詳細情報

• CRID: 1572543026758494848
• NII論文ID: 110001798184
• NII書誌ID: AN1047681X
• ISSN: 13409662
• 本文言語コード: en
• データソース種別:
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