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MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNALys and premature translation termination
Abstract
We have investigated the pathogenetic mechanism of the mitochondrial tRNA(Lys) gene mutation (position 8344) associated with MERRF encephalomyopathy in several mitochondrial DNA (mtDNA)-less cell transformants carrying the mutation and in control cells. A decrease of 50-60% in the specific tRNA(Lys) aminoacylation capacity per cell was found in mutant cells. Furthermore, several lines of evidence reveal that the severe protein synthesis impairment in MERRF mutation-carrying cells is due to premature termination of translation at each or near each lysine codon, with the deficiency of aminoacylated tRNA(Lys) being the most likely cause of this phenomenon.
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“Finally, decreased mt-tRNA stability has been described with the m.8344A N G mutation both in vitro and in cybrid osteosarcoma cells [198,202].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [202]
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Metadata
- Authors
- Enriquez, J. A., Chomyn, A., & Attardi, G.
- Affiliations
- California Institute of Technology (US)
- ORCID
- Attardi, Giuseppe
- Venue
- Nature Genetics
- Published
- 1995-05
- Volume
- 10
- Issue
- 1
- Pages
- 47-55
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2043779724
- Cited by
- 285
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 5 · 2016: 8 · 2015: 13 · 2014: 7 · 2013: 6 · 2012: 12
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM11726)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- MERRF syndrome, mitochondrial DNA mutations, tRNALys, aminoacylation, mitochondrial encephalomyopathy, pathogenesis
- MeSH terms
- Cell Line, DNA, Mitochondrial, Humans, Lysine, Methionine, Mitochondria, Mutation, NADH Dehydrogenase, Oxygen Consumption, Peptide Chain Termination, Translational, Ribosomes, RNA, Transfer, Amino Acyl, RNA, Transfer, Lys, Transformation, Genetic, Protein Biosynthesis, MERRF Syndrome
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