CRM1 介导成熟 microRNAs 的核质穿梭。
CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs.
机构信息
Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91010, USA.
出版信息
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21655-9. doi: 10.1073/pnas.0912384106. Epub 2009 Dec 2.
Abstract
Drosha-processed microRNAs (miRNAs) have been shown to be exported from the nucleus to the cytoplasm by Exportin 5, where they are processed a second time to generate mature miRNAs. In this work we show that miRNAs also use CRM1 for nuclear-cytoplasmic shuttling. Inhibition of CRM1 by Leptomycin B results in nuclear accumulation of miRNA guide sequences. Nuclear to cytoplasmic transport can be actively competed by synthetic small interfering RNAs, indicating that this pathway is shared by different classes of processed small RNAs. We also find that CRM1 coimmunoprecipitates with Ago-1, Ago-2, Topo2alpha, EzH2, and Mta, consistent with a role of Argonautes and small RNAs in chromatin remodeling.
摘要
Drosha 处理的 microRNAs (miRNAs) 已被证明通过 Exportin 5 从细胞核输出到细胞质，在那里它们被进一步加工生成成熟的 miRNAs。在这项工作中，我们表明 miRNAs 也使用 CRM1 进行核质穿梭。CRM1 的抑制剂 Leptomycin B 导致 miRNA 引导序列在核内积累。核质运输可以被合成的小干扰 RNA 主动竞争，表明不同种类的加工小 RNA 共享此途径。我们还发现 CRM1 与 Ago-1、Ago-2、Topo2alpha、EzH2 和 Mta 共免疫沉淀，这与 Argonautes 和小 RNA 在染色质重塑中的作用一致。
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