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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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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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
- hybrid
- doi.org
- Licence
- 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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