Cited by 15RNA and protein synthesis mechanismsMitochondrial Function and PathologyRNA modifications and cancer

The pathogenic A4269G mutation in human mitochondrial tRNAIle alters the T‐stem structure and decreases the binding affinity for elongation factor Tu

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Hino, Narumi, Suzuki, Tsutomu, Yasukawa, Takehiro, Seio, Kohji, Watanabe, Kimitsuna, Ueda, Takuya·2004·Genes to Cells

Abstract

The A4269G mutation in the human mitochondrial (mt) tRNA(Ile) gene is associated with fatal cardiomyopathy. This mutation completely inhibits protein synthesis in mitochondria, thereby significantly reducing their respiratory activity. The steady-state amount of tRNA(Ile) in cells bearing the A4269G mutation is almost half that of control cells. We previously reported that this mutation causes tRNA(Ile) to be unstable both in vivo and in vitro. To investigate whether the instability of the mutant tRNA(Ile) is due to structural alterations, a nuclease-probing experiment was performed with a mitochondrial enzymatic extract, which showed that the A4269G mutation destabilizes the T-stem of the mutant tRNA(Ile). In addition, measurements of the binding affinity of the aminoacylated mutant tRNA(Ile) for mt elongation factor Tu (EF-Tu) showed that the mutant tRNA(Ile) binds mt EF-Tu less efficiently than the wild-type does. This observation provides insight into the molecular pathology associated with tRNA dysfunction caused by this pathogenic point mutation.

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Crossref · 10.1111/j.1356-9597.2004.00718.x

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  • m.4269A N G impairs binding affinity for EFTu two-fold by altering mt-tRNA Ile T-stem structure.

    “By altering mt-tRNA Ile T-stem structure, the mutation m.4269A N G impairs binding affinity for EFTu two-fold [205].”

    From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [205]

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Authors
Hino, N., Suzuki, T., Yasukawa, T., Seio, K., Watanabe, K., & Ueda, T.
Affiliations
  • The University of Tokyo (JP)
  • Tokyo Institute of Technology (JP)
Corresponding author
Ueda, Takuya
Venue
Genes to Cells
Publisher
Wiley
Published
2004-03
Volume
9
Issue
3
Pages
243-252
ISSN
  • 1356-9597 (ISSN-L)
  • 1365-2443
OpenAlex
W2073471628
Cited by
15
References
37
Citations by year
2021: 1 · 2020: 2 · 2018: 1 · 2017: 1 · 2013: 1 · 2012: 2
FWCI
0.24
Type
journal article
Language
en
Open access
Locations
  • Genes to Cells (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Tokyo Tech Research Repository (Tokyo Institute of Technology) (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
elongation factor Tu, tRNA stability, mitochondrial cardiomyopathy, mitochondrial protein synthesis inhibition, point mutations, binding affinity
MeSH terms
RNA, Mitochondrial, Base Sequence, HeLa Cells, Humans, Molecular Sequence Data, Cardiomyopathies, Peptide Elongation Factor Tu, Protein Binding, Ribonucleases, RNA, RNA, Transfer, Amino Acyl, RNA, Transfer, Val, Molecular Structure, Point Mutation, RNA Stability, Electrophoretic Mobility Shift Assay, Mitochondrial Diseases

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