The pathogenic A4269G mutation in human mitochondrial tRNAIle alters the T‐stem structure and decreases the binding affinity for elongation factor Tu
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Crystal Structure of the Ternary Complex of Phe-tRNA Phe , EF-Tu, and a GTP Analog
Nissen, P., Kjeldgaard, M., Thirup, S., Polekhina, G., Reshetnikova, L. S., Clark, B. F. C., & Nyborg, J. (1995) · Science · doi:10.1126/science.270.5241.1464 · Cited by 851 · see citing works
Sekiguchi, M. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)83119-2 · Cited by 668 · see citing works
MITOMAP: a human mitochondrial genome database--2004 update
Brandon, M. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki079 · Cited by 568 · see citing works
Suzuki, T., Suzuki, T., Wada, T., Saigo, K., & Watanabe, K. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf656 · Cited by 388 · see citing works
Self-citationYasukawa, T., Suzuki, T., Suzuki, T., Ueda, T., Ohta, S., & Watanabe, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.6.4251 · Cited by 268 · see citing works
Self-citationWobble modification defect in tRNA disturbs codon–anticodon interaction in a mitochondrial disease
Yasukawa, T., Suzuki, T., Ishii, N., Ohta, S., & Watanabe, K. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.4794 · Cited by 240 · see citing works
Self-citationMitochondrial tRNAlle mutation in fatal cardiomyopathy
Taniike, M., Fukushima, H., Yanagihara, I., et al. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)80773-9 · Cited by 163 · see citing works
Ternary Complex Formation between Elongation Factor Tu, GTP and Aminoacyl-tRNA: an Equilibrium Study
Pingoud, A. M., Urbanke, C., Krauss, G., et al. (1977) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1977.tb11752.x · Cited by 131 · see citing works
Cupric ion catalysis in hydrolysis of aminoacyl-tRNA
Schofield, P. R., & Zamecnik, P. C. (1968) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(68)90185-8 · Cited by 129 · see citing works
Identification and Characterization of Mammalian Mitochondrial tRNA nucleotidyltransferases
Nagaike, T., Suzuki, T., Tomari, Y., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106202200 · Cited by 129 · see citing works
Self-citationYasukawa, T., Suzuki, T., Ishii, N., Ueda, T., Ohta, S., & Watanabe, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01145-5 · Cited by 124 · see citing works
Self-citationKaneko, T., Suzuki, T., Kapushoc, S. T., Rubio, M. A., Ghazvini, J., Watanabe, K., Simpson, L., & Suzuki, T. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg066 · Cited by 113 · see citing works
Self-citationMITOMAP: a human mitochondrial genome database--1998 update
Kogelnik, A. M. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.112 · Cited by 112 · see citing works
Post-transcriptional regulation of the steady-state levels of mitochondrial tRNAs in HeLa cells
King, M. P., & Attardi, G. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82194-9 · Cited by 104 · see citing works
Spremulli, L. L., & Schwartzbach, C. J. (2021) · PubMed · doi:10.17615/7m2f-aj33 · Cited by 89 · see citing works
Woriax, V. L., Burkhart, W., & Spremulli, L. L. (1995) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(95)00176-x · Cited by 80 · see citing works
Hayashi, J., Ohta, S., Kagawa, Y., Takai, D., Miyabayashi, S., Tada, K., Fukushima, H., Inui, K., Okada, S., & Goto, Y. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32274-3 · Cited by 78 · see citing works
Kiesewetter, S., Ott, G., & Sprinzl, M. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.16.4677 · Cited by 68 · see citing works
Feuermann, M., Francisci, S., Rinaldi, T., De Luca, C., Rohou, H., Frontali, L., & Bolotin‐Fukuhara, M. (2003) · The EMBO Reports · doi:10.1038/sj.embor.embor713 · Cited by 67 · see citing works
Interaction of Mitochondrial Elongation Factor Tu with Aminoacyl-tRNA and Elongation Factor Ts
Cai, Y.-C., Bullard, J. M., Thompson, N. L., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001899200 · Cited by 66 · see citing works
Levinger, L. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg282 · Cited by 66 · see citing works
High resolution crystal structure of bovine mitochondrial EF-tu in complex with GDP
Andersen, G. R., Thirup, S., Spremulli, L. L., et al. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3564 · Cited by 64 · see citing works
Hanada, T., Suzuki, T., Yokogawa, T., et al. (2001) · Genes to Cells · doi:10.1046/j.1365-2443.2001.00491.x · Cited by 62 · see citing works
Self-citationDegoul, F. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.3.347 · Cited by 62 · see citing works
Wu, X., & RajBhandary, U. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.3.1891 · Cited by 61 · see citing works
Chemical Deprotection Strategy for the Elaboration of Misacylated Transfer RNA's
Lodder, M., Golovine, S. Y., & Hecht, S. M. (1997) · The Journal of Organic Chemistry · doi:10.1021/jo962170t · Cited by 60 · see citing works
Functional defects of pathogenic human mitochondrial tRNAs related to structural fragility.
Kelley, S. O., SCHIMMEL, P. R., & Steinberg, S. V. (2000) · Nature Structural Biology · doi:10.1038/79612 · Cited by 58 · see citing works
MITOMAP: an update on the status of the human mitochondrial genome database
Kogelnik, A. M., Lott, M. T., Brown, M. D., et al. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.1.196 · Cited by 53 · see citing works
A pathogenic point mutation reduces stability of mitochondrial mutant tRNAIle
Yasukawa, T. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.19.3779 · Cited by 48 · see citing works
Self-citationFoürster, C., Chakraburtty, K., & Sprinzl, M. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.24.5679 · Cited by 44 · see citing works
Contributions of the Individual Domains in Human La Protein to Its RNA 3′-End Binding Activity
Ohndorf, U., Steegborn, C., Knijff, R., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102891200 · Cited by 41 · see citing works
Decreased CCA-addition in Human Mitochondrial tRNAs Bearing a Pathogenic A4317G or A10044G Mutation
Tomari, Y., Hino, N., Nagaike, T., Suzuki, T., & Ueda, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213216200 · Cited by 40 · see citing works
Self-citationKelley, S. O., Steinberg, S. V., & SCHIMMEL, P. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008320200 · Cited by 39 · see citing works
Isoleucyl initiator tRNA does not initiate eucaryotic protein synthesis.
Wagner, T., Gross, M., & Sigler, P. B. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42903-6 · Cited by 33 · see citing works
Molecular Investigations on tRNAs Involved in Human Mitochondrial Disorders
Florentz, C. (2002) · Bioscience Reports · doi:10.1023/a:1016065107165 · Cited by 32 · see citing works
Stortchevoi, A., Varshney, U., & RajBhandary, U. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212890200 · Cited by 21 · see citing works
Purification and crystallization of the ternary complex of elongation factor Tu:GTP and Phe‐tRNAPhe
Nissen, P., Reshetnikova, L. S., Siboska, G. E., et al. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01254-7 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial DNA mutations and human disease
Tuppen, H. A. L., Blakely, E. L., Turnbull, D. M., & Taylor, R. W. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.005 · Cited by 676 · see citing works
“4269ANG impairs binding affinity for EFTu two-fold [205].”
Background
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review