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. © 2013 European Cystic Fibrosis Society.
Altamura, N., Castaldo, R., Finotti, A., Breveglieri, G., Salvatori, F., Zuccato, C., … Borgatti, M. (2013). Tobramycin is a suppressor of premature termination codons. Journal of Cystic Fibrosis, 12(6), 806–811. https://doi.org/10.1016/j.jcf.2013.02.007