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Citations to this article

Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin
Liat Linde, … , Eitan Kerem, Batsheva Kerem
Liat Linde, … , Eitan Kerem, Batsheva Kerem
Published March 1, 2007
Citation Information: J Clin Invest. 2007;117(3):683-692. https://doi.org/10.1172/JCI28523.
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Research Article Pulmonology Article has an altmetric score of 9

Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin

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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.

Authors

Liat Linde, Stephanie Boelz, Malka Nissim-Rafinia, Yifat S. Oren, Michael Wilschanski, Yasmin Yaacov, Dov Virgilis, Gabriele Neu-Yilik, Andreas E. Kulozik, Eitan Kerem, Batsheva Kerem

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 Total
Citations: 1 5 10 8 14 14 12 11 7 8 4 7 9 7 6 7 4 8 2 144
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2012 (7)

Title and authors Publication Year
Class 1 CF Mutations
M Wilschanski
Frontiers in pharmacology 2012
Readthrough strategies for therapeutic suppression of nonsense mutations in inherited metabolic disease
B Pérez, P Rodríguez-Pombo, M Ugarte, LR Desviat
Molecular syndromology 2012
Rescue of nonsense mutations by amlexanox in human cells
S Gonzalez-Hilarion, T Beghyn, J Jia, N Debreuck, G Berte, K Mamchaoui, V Mouly, DC Gruenert, B Déprez, F Lejeune
Orphanet Journal of Rare Diseases 2012
The GABRG2 nonsense mutation, Q40X, associated with Dravet syndrome activated NMD and generated a truncated subunit that was partially rescued by aminoglycoside-induced stop codon read-through
X Huang, M Tian, CC Hernandez, N Hu, RL Macdonald
Neurobiology of Disease 2012
Suppression of premature termination codons as a therapeutic approach
KM Keeling, D Wang, SE Conard, DM Bedwell
Critical Reviews in Biochemistry and Molecular Biology 2012
The intronic GABRG2 mutation, IVS6+2T->G, associated with childhood absence epilepsy altered subunit mRNA intron splicing, activated nonsense-mediated decay, and produced a stable truncated γ2 subunit
M Tian, RL Macdonald
The Journal of neuroscience : the official journal of the Society for Neuroscience 2012
Cystic fibrosis transmembrane conductance regulator dysfunction and its treatment
J Hull
Journal of the Royal Society of Medicine 2012

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