Université Lille Nord de France, IFR142, Lille, France.
Orphanet J Rare Dis. 2012 Aug 31;7:58. doi: 10.1186/1750-1172-7-58.
Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough.
Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs.
We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional.
As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.
无义突变是许多癌症和遗传性疾病的起源。无义突变的后果通常是由于一种称为无义介导的 mRNA 降解（NMD）的 mRNA 监测机制的激活，导致突变基因表达缺失。已经开发了一些挽救含有无义突变的 mRNA 表达的策略，例如 NMD 抑制或无义突变通读。
我们使用专门的筛选系统，寻找能够阻断 NMD 的分子。此外，我们还使用了 3 种源自患者细胞并携带无义突变的细胞系，研究所选分子对无义突变 mRNA 水平和这些突变 mRNA 合成蛋白质的影响。
我们在这里证明，安米诺素，一种已使用数十年的药物，不仅能诱导治疗细胞中无义突变 mRNA 含量增加，还能有效地合成全长蛋白。我们还证明这些全长蛋白是有功能的。
由于这种双重作用，安米诺素可能可用于治疗由无义突变引起的疾病。
