Cited by 268RNA and protein synthesis mechanismsMitochondrial Function and PathologyRNA modifications and cancer

Modification Defect at Anticodon Wobble Nucleotide of Mitochondrial tRNAsLeu(UUR) with Pathogenic Mutations of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

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Yasukawa, Takehiro, Suzuki, Tsutomu, Suzuki, Takeo, Ueda, Takuya, Ohta, Shigeo, Watanabe, Kimitsuna·2000·Journal of Biological Chemistry

Abstract

The mitochondrial tRNA(Leu)(UUR) (R = A or G) gene possesses several hot spots for pathogenic mutations. A point mutation at nucleotide position 3243 or 3271 is associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes and maternally inherited diabetes with deafness. Detailed studies on two tRNAs(Leu)(UUR) with the 3243 or 3271 mutation revealed some common characteristics in cybrid cells: (i) a decreased life span, resulting in a 70% decrease in the amounts of the tRNAs in the steady state, (ii) a slight decrease in the ratios of aminoacyl-tRNAs(Leu)(UUR) versus uncharged tRNAs(Leu)(UUR), and (iii) accurate aminoacylation with leucine without any misacylation. As a marked result, both of the mutant tRNA molecules were deficient in a modification of uridine that occurs in the normal tRNA(Leu)(UUR) at the first position of the anticodon. The lack of this modification may lead to the mistranslation of leucine into non-cognate phenylalanine codons by mutant tRNAs(Leu)(UUR), according to the mitochondrial wobble rule, and/or a decrease in the rate of mitochondrial protein synthesis. This finding could explain why two different mutations (3243 and 3271) manifest indistinguishable clinical features.

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Crossref · 10.1074/jbc.275.6.4251

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  • m.3243A N G prevents taurine modification of the anticodon wobble position (U34) in cybrid HeLa cells.

    “but to prevent taurine modification of the anticodon wobble position (U34) in cybrid HeLa cells [197].”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [197]

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Authors
Yasukawa, T., Suzuki, T., Suzuki, T., Ueda, T., Ohta, S., & Watanabe, K.
Affiliations
  • The University of Tokyo (JP)
  • Nippon Medical School (JP)
Corresponding author
  • Ohta, Shigeo
  • Watanabe, Kimitsuna
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-02
Volume
275
Issue
6
Pages
4251-4257
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2075835114
Cited by
268
References
45
Citations by year
2026: 3 · 2025: 8 · 2024: 11 · 2023: 10 · 2022: 10 · 2021: 15 · 2020: 14 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 15 · 2013: 6 · 2012: 10
FWCI
5.29
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
MERRF, maternally inherited diabetes and deafness, aminoacylation, aminoacyl-tRNA, cybrid cells, mitochondrial translation, codon recognition
MeSH terms
RNA, Mitochondrial, Anticodon, Base Sequence, Cell Line, DNA, Mitochondrial, HeLa Cells, Humans, Molecular Sequence Data, Nucleosides, RNA, RNA, Transfer, Leu, Mass Spectrometry, MELAS Syndrome, Point Mutation, Sequence Analysis

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