Disruption of GW bodies impairs mammalian RNA interference
Disruption of GW bodies impairs mammalian RNA interference
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DOI：
10.1038/ncb1334
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发表时间：
2005-12-01
影响因子：
21.3
通讯作者：
Chan, EKL
中科院分区：
文献类型：
--
作者：
Jakymiw, A;Lian, SL;Chan, EKL
GW182 RNA 结合蛋白最初被证明与特定的 mRNA 子集相关，并驻留在称为 GW 小体 (GWB)(1) 的离散细胞质灶内。 GWB 富含参与 mRNA 降解的蛋白质 (2)。最近的报告表明，外源引入的人类 Argonaute-2 (Ago2) 也富含 GWB，表明 RNA 干扰功能可能以某种方式与这些结构相关 (3,4)。在本报告中，我们证明内源 Agog 和转染的小干扰 RNA (siRNA) 也存在于这些相同的细胞质体内，并且 GW182 蛋白与 Agog 相互作用。 HeLa 细胞中这些细胞质灶的破坏会干扰核纤层蛋白-A/C 特异性 siRNA 的沉默能力。我们的数据支持一个模型，其中 GW182 和/或细胞质 GWB 的微环境有助于 RNA 诱导的沉默复合物和 RNA 沉默。
The GW182 RNA-binding protein was initially shown to associate with a specific subset of mRNAs and to reside within discrete cytoplasmic foci named GW bodies (GWBs)(1). GWBs are enriched in proteins that are involved in mRNA degradation(2). Recent reports have shown that exogenously introduced human Argonaute-2 (Ago2) is also enriched in GWBs, indicating that RNA interference function may be somehow linked to these structures(3,4). In this report, we demonstrate that endogenous Agog and transfected small interfering RNAs (siRNAs) are also present within these same cytoplasmic bodies and that the GW182 protein interacts with Agog. Disruption of these cytoplasmic foci in HeLa cells interferes with the silencing capability of a siRNA that is specific to lamin-A/C. Our data support a model in which GW182 and/or the microenvironment of the cytoplasmic GWBs contribute to the RNA-induced silencing complex and to RNA silencing.