Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies, University of Palermo, 90128 Palermo, Italy.
Int J Mol Sci. 2023 Jun 1;24(11):9609. doi: 10.3390/ijms24119609.
Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations that generate a premature termination codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ribosome's capacity to skip a PTC, thus generating a full-length protein. "TRIDs" are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We investigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2'-O-methyltransferase.
囊性纤维化（CF）是一种常染色体隐性遗传疾病，由 CFTR 基因突变引起，该基因编码 CFTR 氯离子通道。大约 10%的 CFTR 基因突变是“停止”突变，产生过早终止密码子（PTC），从而合成截短的 CFTR 蛋白。一种绕过 PTC 的方法依赖于核糖体通读，即核糖体跳过 PTC 的能力，从而产生全长蛋白。“TRIDs”是发挥核糖体通读的分子；对于某些分子，其作用机制仍存在争议。我们通过计算机分析和体外研究来研究我们最近合成的 TRIDs，即 NV848、NV914 和 NV930，发挥其通读活性的可能作用机制（MOA）。我们的结果表明，它们可能抑制色氨酸 tRNA 特异性 2'-O-甲基转移酶 FTSJ1。
