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J Cyst Fibros. 2013 Dec;12(6):806-11. doi: 10.1016/j.jcf.2013.02.007. Epub 2013 Mar 27.

Tobramycin is a suppressor of premature termination codons.

Author information

1
Institute of Biomembranes and Bioenergetics, CNR, Via Amendola 165/A, 70126 Bari, Italy. Electronic address: n.altamura@ibbe.cnr.it.

Abstract

Premature translation terminations (PTCs) constitute the molecular basis of many genetic diseases, including cystic fibrosis, as they lead to the synthesis of truncated non-functional or partially functional protein. Suppression of translation terminations at PTCs (read-through) has been developed as a therapeutic strategy to restore full-length protein in several genetic diseases. Phenotypic consequences of PTCs can be exacerbated by the nonsense-mediated mRNA decay (NMD) pathway that detects and degrades mRNA containing PTC. Modulation of NMD, therefore, is also of interest as a potential target for the suppression therapy. Tobramycin is an aminoglycoside antibiotic, normally used to treat Pseudomonas aeruginosa pulmonary infection in CF patients. In the present study, by using yeast as a genetic system, we have examined the ability of Tobramycin to suppress PTCs as a function of the presence or absence of NMD. Results demonstrate that Tobramycin exhibits read-through ability on PTCs and preferentially in absence of NMD.

KEYWORDS:

Aminoglycoside antibiotics; CF; CFTR; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic fibrosis; NMD; PTCs; RLUs; Read-through; SD; Tobramycin; Yeast; cystic fibrosis; nonsense-mediated mRNA decay; premature termination codons; relative light units; standard deviation

PMID:
23540394
DOI:
10.1016/j.jcf.2013.02.007
[Indexed for MEDLINE]
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