ArticleNucleic acids research2014
Why base tautomerization does not cause errors in mRNA decoding on the ribosome.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Mechanism of Ligand Discrimination by theJournal of chemical information and modeling · 2023Article
- Constraints on error rate revealed by computational study of G•U tautomerization in translation.Nucleic acids research · 2021Article
- Multiscale Modeling of Wobble to Watson-Crick-Like Guanine-Uracil Tautomerization Pathways in RNA.International journal of molecular sciences · 2021Article
- Broad range of missense error frequencies in cellular proteins.Nucleic acids research · 2019Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
- Origin of the omnipotence of eukaryotic release factor 1.Nature communications · 2017Article
- A recent intermezzo at the Ribosome Club.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Ribosome dynamics during decoding.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- How EF-Tu can contribute to efficient proofreading of aa-tRNA by the ribosome.Nature communications · 2016Article
- An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.The Journal of biological chemistry · 2016Article
- Accuracy of initial codon selection by aminoacyl-tRNAs on the mRNA-programmed bacterial ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Structural insights into the translational infidelity mechanism.Nature communications · 2015Article
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2 authors.
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Abstract
The structure of the genetic code implies strict Watson-Crick base pairing in the first two codon positions, while the third position is known to be degenerate, thus allowing wobble base pairing. Recent crystal structures of near-cognate tRNAs accommodated into the ribosomal A-site, however, show canonical geometry even with first and second position mismatches. This immediately raises the question of whether these structures correspond to tautomerization of the base pairs. Further, if unusual tautomers are indeed trapped why do they not cause errors in decoding? Here, we use molecular dynamics free energy calculations of ribosomal complexes with cognate and near-cognate tRNAs to analyze the structures and energetics of G-U mismatches in the first two codon positions. We find that the enol tautomer of G is almost isoenergetic with the corresponding ketone in the first position, while it is actually more stable in the second position. Tautomerization of U, on the other hand is highly penalized. The presence of the unusual enol form of G thus explains the crystallographic observations. However, the calculations also show that this tautomer does not cause high codon reading error frequencies, as the resulting tRNA binding free energies are significantly higher than for the cognate complex.
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