ArticleThe Journal of clinical investigation2007
Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
150 citing papers in PubMed, 292 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
- Gentamicin Induces Laminin 332 and Improves Wound Healing in Junctional Epidermolysis Bullosa Patients with Nonsense Mutations.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Trial
- Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients.The Journal of clinical investigation · 2017Trial
- Trial
- A Translational Roadmap for Neurological Nonsense Mutation Disorders.International journal of molecular sciences · 2026Review
- An engineered UGA suppressor tRNA gene for disease-agnostic AAV delivery.Nature biotechnology · 2026Article
- Barriers to the Pharmacologic Rescue of W1282X CFTR.Biochemistry · 2026Article
- Case Report: Diagnostic odyssey in rare diseases: when genetic variants are misinterpreted.Frontiers in pediatrics · 2026Article
- AAV-delivered engineered suppressor tRNA rescues visual function in mice with an inherited retinal disease.Nature communications · 2025Article
- Article
- Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals.Genome biology · 2025Article
- Mechanisms suppressing noncoding translation.Trends in cell biology · 2025Review
- Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.RNA (New York, N.Y.) · 2025Review
- 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
- Suppressor tRNA in gene therapy.Science China. Life sciences · 2024Review
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- tRNA therapeutics for genetic diseases.Nature reviews. Drug discovery · 2024Review
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development.Nature communications · 2023Article
- Combining nonsense mutation suppression therapy with nonsense-mediated decay inhibition in neurofibromatosis type 1.Molecular therapy. Nucleic acids · 2023Article
90 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
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycosides can readthrough premature termination codons (PTCs), permitting translation of full-length proteins. Previously we have found variable efficiency of readthrough in response to the aminoglycoside gentamicin among cystic fibrosis (CF) patients, all carrying the W1282X nonsense mutation. Here we demonstrate that there are patients in whom the level of CF transmembrane conductance regulator (CFTR) nonsense transcripts is markedly reduced, while in others it is significantly higher. Response to gentamicin was found only in patients with the higher level. We further investigated the possibility that the nonsense-mediated mRNA decay (NMD) might vary among cells and hence governs the level of nonsense transcripts available for readthrough. Our results demonstrate differences in NMD efficiency of CFTR transcripts carrying the W1282X mutation among different epithelial cell lines derived from the same tissue. Variability was also found for 5 physiologic NMD substrates, RPL3, SC35 1.6 kb, SC35 1.7 kb, ASNS, and CARS. Importantly, our results demonstrate the existence of cells in which NMD of all transcripts was efficient and others in which the NMD was less efficient. Downregulation of NMD in cells carrying the W1282X mutation increased the level of CFTR nonsense transcripts and enhanced the CFTR chloride channel activity in response to gentamicin. Together our results suggest that the efficiency of NMD might vary and hence have an important role in governing the response to treatments aiming to promote readthrough of PTCs in many genetic diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.