Inhibition of translation by RNA-small molecule interactions
Inhibition of translation by RNA-small molecule interactions
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DOI：
10.1017/s135583820202633x
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发表时间：
2002-04-01
期刊：
影响因子：
4.5
通讯作者：
Pelletier, J
中科院分区：
文献类型：
--
作者：
Harvey, I;Garneau, P;Pelletier, J
小分子配体-RNA相互作用有可能在多个步骤和以多种方式影响基因表达。在这里，我们证明了这种相互作用是足够稳定的，以抑制真核生物的mRNA在体外和体内的翻译。仅当靶向mRNA的5' UTR时观察到抑制，并且响应与该区域内的结合位点的数量成比例。我们发现，小分子配体-RNA相互作用可以足够稳定，以防止80 S核糖体组装在mRNA模板上。用小分子配体特异性消除限定mRNA表达的能力证明了旨在控制特异性mRNA翻译的药理学靶向的原理证明。
Small molecule ligand-RNA interactions have the potential to influence gene expression at a variety of steps and in a number of ways. Here, we demonstrate that such interactions are sufficiently stable to inhibit translation of eukaryotic mRNAs in vitro and in vivo. Inhibition is only observed when the 5' UTR of the mRNA is targeted, and the response is proportional to the number of binding sites within this region. We find that small molecule ligand-RNA Interactions can be sufficiently stable to prevent 80S ribosome assembly on an mRNA template. The ability to specifically ablate expression of a defined mRNA with a small molecule ligand demonstrates proof of principle for pharmacological targeting aimed at controlling translation of specific mRNAs.