Cited by 99RNA modifications and cancerRNA and protein synthesis mechanismsMitochondrial Function and Pathology

Search for differences in post-transcriptional modification patterns of mitochondrial DNA-encoded wild-type and mutant human tRNALys and tRNALeu(UUR)

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Helm, M., Florentz, C., Chomyn, A., Attardi, G.·1999·Nucleic Acids Research

Abstract

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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Crossref · 10.1093/nar/27.3.756

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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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Research works printed but not linked: 7

  1. Björk,G.R. (1995) In Söll,D. and RajBhandary,U.L. (eds) tRNA: Structure, Biosynthesis and Function. American Society for Microbiology Press, Washington, DC, pp. 165-205.
  2. Keith,G. (1990) In Gehrke,C.W. and Kuo,K.C.T. (eds), Chromatography and Modification of Nucleosides. Elsevier, Amsterdam, The Netherlands, Vol. 45A, pp. A103-A141.
  3. Villani,G. and Attardi,G. (1997) Proc. Natl Acad. Sci. USA, 94, 1166-1171.
  4. Chomyn,A., Martinuzzi,A., Yoneda,M., Daga,A., Hurko,O., Johns,D., Lai,S.T., Nonaka,I., Angelini,C. and Attardi,G. (1992) Proc. Natl Acad. Sci. USA, 89, 4221-4225.
  5. Mörl,M., Dorner,M. and Pääbo,S. (1994) In Uhlén,M., Hornes,E. and Olsvik,O. (eds), Advances in Biomagnetic Separation. Eaton Publishing, Natik, MA, pp. 107-111.
  6. Winkler,M.E. (1998) In Grosjean,H. and Benne,R. (eds), Modification and Editing of RNA. American Society for Microbiology Press, Washington, DC, pp. 441-469.
  7. Björk,G.R. and Rasmuson,T. (1998) In Grosjean,H. and Benne,R. (eds), Modification and Editing of RNA. American Society for Microbiology Press, Washington, DC, pp. 471-491.

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Authors
Helm, M., Florentz, C., Chomyn, A., & Attardi, G.
Affiliations
California Institute of Technology (US)
Venue
Nucleic Acids Research
Published
1999-02-01
Volume
27
Issue
3
Pages
756-763
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
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
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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