ArticleHuman molecular genetics2017
Identification of the amino acids inserted during suppression of CFTR nonsense mutations and determination of their functional consequences.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 94 citations in OpenAlex.
- Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: The international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF).Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Trial
- RNAViruses · 2026Review
- Identification of small molecules that enhance aminoglycoside-mediated suppression ofMolecular therapy. Oncology · 2026Article
- Glutamine codon-driven translational readthrough reveals context-dependent stop codon decoding fidelity.bioRxiv : the preprint server for biology · 2026Article
- RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations.Cellular and molecular life sciences : CMLS · 2026Article
- Anticodon-edited transfer RNAs (ACE-tRNAs) encoded as therapeutic nonviral minimal DNA vectors.Nucleic acids research · 2026Article
- Ribosomal read through as an alternative therapy for patients with hemophilia with nonsense mutations.Journal of thrombosis and haemostasis : JTH · 2026Article
- Identity, functional consequences, and context effects of amino acids inserted during suppression of CFTR nonsense mutations.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Article
- Anticodon Edited Transfer RNAs (ACE-tRNAs) Encoded as Therapeutic Nonviral Minimal DNA Vectors.bioRxiv : the preprint server for biology · 2025Article
- ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis.Nucleic acids research · 2025Article
- Ophthalmologic Manifestations in Bardet-Biedl Syndrome: Emerging Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- An engineered glutamic acid tRNA for efficient suppression of pathogenic nonsense mutations.Nucleic acids research · 2025Article
- Adenine base editing of CFTR using receptor targeted nanoparticles restores function to G542X cystic fibrosis airway epithelial cells.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Selective amino acid formulation enhances anion secretion and restores function in cystic fibrosis mutations.Frontiers in pharmacology · 2025Article
- A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025Article
- Optimization of ACE-tRNAs function in translation for suppression of nonsense mutations.Nucleic acids research · 2024Article
- Efficient suppression of premature termination codons with alanine by engineered chimeric pyrrolysine tRNAs.Nucleic acids research · 2024Article
- Gene Dosage ofGenes · 2024Article
- Extended stop codon context predicts nonsense codon readthrough efficiency in human cells.Nature communications · 2024Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
In-frame premature termination codons (PTCs) account for ∼11% of all disease-associated mutations. PTC suppression therapy utilizes small molecules that suppress translation termination at a PTC to restore synthesis of a full-length protein. PTC suppression is mediated by the base pairing of a near-cognate aminoacyl-tRNA with a PTC and subsequently, the amino acid becomes incorporated into the nascent polypeptide at the site of the PTC. However, little is known about the identity of the amino acid(s) inserted at a PTC during this process in mammalian cells, or how the surrounding sequence context influences amino acid incorporation. Here, we determined the amino acids inserted at the cystic fibrosis transmembrane conductance regulator (CFTR) W1282X PTC (a UGA codon) in the context of its three upstream and downstream CFTR codons during G418-mediated suppression. We found that leucine, cysteine and tryptophan are inserted during W1282X suppression. Interestingly, these amino acids (and their proportions) are significantly different from those recently identified following G418-mediated suppression of the CFTR G542X UGA mutation. These results demonstrate for the first time that local mRNA sequence context plays a key role in near-cognate aminoacyl-tRNA selection during PTC suppression. We also found that some variant CFTR proteins generated by PTC suppression exhibit reduced maturation and activity, indicating the complexity of nonsense suppression therapy. However, both a CFTR corrector and potentiator enhanced activity of protein variants generated by G418-mediated suppression. These results suggest that PTC suppression in combination with CFTR modulators may be beneficial for the treatment of CF patients with PTCs.
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Registered trials
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.