title: Tobramycin is a suppressor of premature termination codons.
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.
authors.affiliation: Institute of Biomembranes and Bioenergetics, CNR, Via Amendola 165/A, 70126 Bari, Italy. Electronic address: n.altamura@ibbe.cnr.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Altamura
authors.forename: Rosa
authors.initials: R
authors.lastname: Castaldo
authors.forename: Alessia
authors.initials: A
authors.lastname: Finotti
authors.forename: Giulia
authors.initials: G
authors.lastname: Breveglieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Salvatori
authors.forename: Cristina
authors.initials: C
authors.lastname: Zuccato
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Giulia Chiara
authors.initials: GC
authors.lastname: Panin
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D018389:Codon, Nonsense / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D017930:Genes, Reporter; D005839:Gentamicins / Q000494:pharmacology; D008957:Models, Genetic; D059365:Nonsense Mediated mRNA Decay / Q000187:drug effects* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013489:Suppression, Genetic / Q000187:drug effects* / Q000235:genetics; D014031:Tobramycin / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D018389:Codon, Nonsense; D005839:Gentamicins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014031:Tobramycin
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