Search for differences in post-transcriptional modification patterns of mitochondrial DNA-encoded wild-type and mutant human tRNALys and tRNALeu(UUR)
Open accessAbstract
Post-transcriptional modifications are characteristic features of tRNAs and have been shown in a number of cases to influence both their structural and functional properties, including structure stabilization, amino-acylation and codon recognition. We have developed an approach which allows the investigation of the post-transcriptional modification patterns of human mitochondrial wild-type and mutant tRNAs at both the qualitative and the quantitative levels. Specific tRNA species are long-term labeled in vivo with [32P]orthophosphate, isolated in a highly selective way, enzymatically digested to mononucleotides and then subjected to two-dimensional thin layer chromatographic analysis. The wild-type tRNALysand the corresponding tRNALyscarrying the A8344G mutation associated with the MERRF (Myoclonic Epilepsy with Ragged Red Fibers) syndrome exhibit the same modified nucleotides at the same molar concentrations. By contrast, a quantitatively different modification pattern was observed between the wild-type tRNALeu(UUR)and its counterpart carrying the A3243G mutation associated with the MELAS (Mitochondrial Myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes) syndrome, the latter exhibiting a 50% decrease in m2G content. Complementary sequencing of tRNALeu(UUR)has allowed the localization of this modification at position 10 within the D-stem of the tRNA. The decreased level of this modification may have important implications for understanding the molecular mechanism underlying the MELAS-associated mitochondrial dysfunction.
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m.3243A N G impairs methylation of mt-tRNA Leu(UUR) in cybrid osteosarcoma cells.
“Interestingly, m.3243A N G has been shown to impair methylation of mt-tRNA Leu(UUR) in cybrid osteosarcoma cells [196]”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [196]
Posttranscriptional modifications of mt-tRNA Lys m.8344A N G mutant mt-tRNAs are dependent on nuclear background.
“Similarly, posttranscriptional modifications of mt-tRNA Lys m.8344A N G mutant mt-tRNAs are also dependent on nuclear background [196,198].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [196]
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- Authors
- Helm, M., Florentz, C., Chomyn, A., & Attardi, G.
- Affiliations
- California Institute of Technology (US)
- ORCID
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-02-01
- Volume
- 27
- Issue
- 3
- Pages
- 756-763
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC148244
- OpenAlex
- W2074934195
- Cited by
- 99
- References
- 44
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- HAL (submittedVersion)
- univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion)
- Funders
- California Institute of Technology
- National Institutes of Health
- National Institute of General Medical Sciences (GM11726)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- 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
- Keywords
- mitochondrial tRNA, tRNALys, MERRF, MELAS, A8344G mutation, A3243G mutation, 5-methylcytidine, D-stem, mitochondrial DNA mutations, mitochondrial dysfunction
- MeSH terms
- Autoradiography, Base Sequence, Cell Line, Chromatography, Thin Layer, DNA, Mitochondrial, Humans, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Protein Processing, Post-Translational, RNA, Transfer, Leu, RNA, Transfer, Lys, MELAS Syndrome, MERRF Syndrome
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