ArticleProceedings of the National Academy of Sciences of the United States of America2008
Quality control despite mistranslation caused by an ambiguous genetic code.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 136 citations in OpenAlex.
- Review
- Article
- Ribosomal RNA methylation by GidB modulates discrimination of mischarged tRNA.bioRxiv : the preprint server for biology · 2026Article
- Mistranslation from an endogenous tRNA variant in human pan-genome cell lines.Nucleic acids research · 2026Article
- Cost of Altered Translation Accuracy Shapes Adaptation to Antibiotics in E. coli.Molecular biology and evolution · 2025Article
- Evolving Escherichia coli to use a tRNA with a non-canonical fold as an adaptor of the genetic code.Nucleic acids research · 2024Article
- Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids.Chemical reviews · 2024Review
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Missense suppressor tRNA therapeutics correct disease-causing alleles by misreading the genetic code.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Article
- Genetically stable kill-switch using "demon and angel" expression construct of essential genes.Frontiers in bioengineering and biotechnology · 2024Article
- Mistranslation of the genetic code by a new family of bacterial transfer RNAs.The Journal of biological chemistry · 2023Article
- Not Quite Lost in Translation: Mistranslation Alters Adaptive Landscape Topography and the Dynamics of Evolution.Molecular biology and evolution · 2023Article
- The tRNA identity landscape for aminoacylation and beyond.Nucleic acids research · 2023Review
- Perseverance of protein homeostasis despite mistranslation of glycine codons with alanine.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates.Genes · 2023Article
- Ribosome-mediated biosynthesis of pyridazinone oligomers in vitro.Nature communications · 2022Article
- Genetic background and mistranslation frequency determine the impact of mistranslating tRNASerUGG.G3 (Bethesda, Md.) · 2022Article
- A novel fluorescent reporter sensitive to serine mis-incorporation.RNA biology · 2022Article
- Impact of queuosine modification of endogenousFrontiers in molecular biosciences · 2022Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A high level of accuracy during protein synthesis is considered essential for life. Aminoacyl-tRNA synthetases (aaRSs) translate the genetic code by ensuring the correct pairing of amino acids with their cognate tRNAs. Because some aaRSs also produce misacylated aminoacyl-tRNA (aa-tRNA) in vivo, we addressed the question of protein quality within the context of missense suppression by Cys-tRNA(Pro), Ser-tRNA(Thr), Glu-tRNA(Gln), and Asp-tRNA(Asn). Suppression of an active-site missense mutation leads to a mixture of inactive mutant protein (from translation with correctly acylated aa-tRNA) and active enzyme indistinguishable from the wild-type protein (from translation with misacylated aa-tRNA). Here, we provide genetic and biochemical evidence that under selective pressure, Escherichia coli not only tolerates the presence of misacylated aa-tRNA, but can even require it for growth. Furthermore, by using mass spectrometry of a reporter protein not subject to selection, we show that E. coli can survive the ambiguous genetic code imposed by misacylated aa-tRNA tolerating up to 10% of mismade protein. The editing function of aaRSs to hydrolyze misacylated aa-tRNA is not essential for survival, and the EF-Tu barrier against misacylated aa-tRNA is not absolute. Rather, E. coli copes with mistranslation by triggering the heat shock response that stimulates nonoptimized polypeptides to achieve a native conformation or to be degraded. In this way, E. coli ensures the presence of sufficient functional protein albeit at a considerable energetic cost.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.