ArticleProceedings of the National Academy of Sciences of the United States of America2015
Nonsense suppression by near-cognate tRNAs employs alternative base pairing at codon positions 1 and 3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 138 citations in OpenAlex.
- RNAViruses · 2026Review
- Immunogenic implications of translational readthrough modulate the association of F8 nonsense mutations with inhibitors in Hemophilia A.Molecular medicine (Cambridge, Mass.) · 2026Article
- RiboScreenBiomedicines · 2026Review
- Regulatory landscape of widespread stop codon readthrough inbioRxiv : the preprint server for biology · 2026Article
- A Ψ-Ψ codon-anticodon pairing in nonsense suppression and translational recoding.Nature chemical biology · 2026Article
- An engineered glutamic acid tRNA for efficient suppression of pathogenic nonsense mutations.Nucleic acids research · 2025Article
- Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor Suppressor Genes.IUBMB life · 2025Review
- Ribosomal A-site interactions with near-cognate tRNAs drive stop codon readthrough.Nature structural & molecular biology · 2025Article
- Translational error in mice increases with ageing in an organ-dependent manner.Nature communications · 2025Article
- Selective amino acid formulation enhances anion secretion and restores function in cystic fibrosis mutations.Frontiers in pharmacology · 2025Article
- Anticodon-edited tRNA enables translational readthrough of COL4A5 premature termination codons.PloS one · 2025Article
- N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation.Nature communications · 2024Article
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Extended stop codon context predicts nonsense codon readthrough efficiency in human cells.Nature communications · 2024Article
- Misincorporations of amino acids in p53 in human cells at artificially constructed termination codons in the presence of the aminoglycoside Gentamicin.Frontiers in genetics · 2024Article
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- A robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid.Nature communications · 2023Article
- Cysteine tRNA acts as a stop codon readthrough-inducing tRNA in the human HEK293T cell line.RNA (New York, N.Y.) · 2023Article
- En route towards a personalized medicine approach: Innovative therapeutic modalities for connective tissue disorders.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- System-wide optimization of an orthogonal translation system with enhanced biological tolerance.Molecular systems biology · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Premature termination codons (PTCs) in an mRNA ORF inactivate gene function by causing production of a truncated protein and destabilization of the mRNA. Readthrough of a PTC allows ribosomal A-site insertion of a near-cognate tRNA, leading to synthesis of a full-length protein from otherwise defective mRNA. To understand the mechanism of such nonsense suppression, we developed a yeast system that allows purification and sequence analysis of full-length readthrough products arising as a consequence of endogenous readthrough or the compromised termination fidelity attributable to the loss of Upf (up-frameshift) factors, defective release factors, or the presence of the aminoglycoside gentamicin. Unlike classical "wobble" models, our analyses showed that three of four possible near-cognate tRNAs could mispair at position 1 or 3 of nonsense codons and that, irrespective of whether readthrough is endogenous or induced, the same sets of amino acids are inserted. We identified the insertion of Gln, Tyr, and Lys at UAA and UAG, whereas Trp, Arg, and Cys were inserted at UGA, and the frequency of insertion of individual amino acids was distinct for specific nonsense codons and readthrough-inducing agents. Our analysis suggests that the use of genetic or chemical means to increase readthrough does not promote novel or alternative mispairing events; rather, readthrough effectors cause quantitative enhancement of endogenous mistranslation events. Knowledge of the amino acids incorporated during readthrough not only elucidates the decoding process but also may allow predictions of the functionality of readthrough protein products.
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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.