Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mol Biol Cell. 2010 May 1;21(9):1462-9. doi: 10.1091/mbc.e09-10-0885. Epub 2010 Mar 17.
Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression; however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.
miRNA 介导的基因调控途径的关键组成部分定位于细胞质处理体（P 体）中。越来越多的证据表明，微观 P 体的存在并不总是miRNA 介导的基因调控所必需的。在这里，我们已经表明，格尔德霉素，一种特征明确的 HSP90 抑制剂，可消除 P 体并显著降低 Argonaute 和 GW182 蛋白水平，但不影响 miRNA 水平和 miRNA 介导的基因抑制效率；然而，它显著损害了 siRNA 的加载和外源性 siRNA 的功效。我们的数据表明，HSP90 蛋白在与 RNA 结合之前将 Argonautes 作为伴侣，并且可能有助于小 RNA 的有效加载。
