Institute of Biomembranes and Bioenergetics, CNR, Via Amendola 165/A, 70126 Bari, Italy.
J Cyst Fibros. 2013 Dec;12(6):806-11. doi: 10.1016/j.jcf.2013.02.007. Epub 2013 Mar 27.
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.
过早翻译终止（PTCs）构成了许多遗传疾病的分子基础，包括囊性纤维化，因为它们导致截短的非功能或部分功能蛋白的合成。抑制 PTC 处的翻译终止（通读）已被开发为一种治疗策略，以在几种遗传疾病中恢复全长蛋白。PTC 引起的表型后果可被无义介导的 mRNA 降解（NMD）途径加剧，该途径可检测并降解含有 PTC 的 mRNA。因此，NMD 的调节也作为抑制治疗的潜在靶标很有意义。妥布霉素是一种氨基糖苷类抗生素，通常用于治疗 CF 患者的铜绿假单胞菌肺部感染。在本研究中，我们通过使用酵母作为遗传系统，检查了妥布霉素抑制 PTC 的能力，作为 NMD 存在与否的功能。结果表明，妥布霉素在 PTC 处具有通读能力，并且在不存在 NMD 的情况下更具优势。
