Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells.
Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells.
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DOI：
10.1093/nar/gkq1216
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发表时间：
2011-04
影响因子：
14.9
通讯作者：
Sczakiel G
中科院分区：
文献类型：
--
作者：
Detzer A;Engel C;Wünsche W;Sczakiel G
人体细胞在受到各种应激时，会产生内源性应激颗粒（SG）。人Argonaute 2（hAgo 2）是RNA诱导的沉默复合物（RISC）的催化核心组分，可以被募集到SG以及P体（PB），表明hAgo 2在SG、PB或其他亚细胞位点的动态细胞内分布可能与RNA干扰（RNAi）机制的效率有关。本文研究了热休克、亚砷酸钠（NaAsO_2）、放线菌酮（CHX）和脂质体介导的硫代磷酸酯（PS）修饰的寡核苷酸（ON）转染对hAgo_2细胞内定位和RNAi效率的影响。荧光显微镜和沉降分析的细胞级分表明，应力诱导的积累hAgo 2在SGs和损失的明显组成的复合物含有hAgo 2或其亚细胞环境。用PS-ON转染细胞诱导细胞应激，其在表型上类似于已建立的诱导剂热休克和NaAsO 2。hAgo 2的细胞内再分布与其增加的代谢稳定性和减少的由microRNA或短干扰RNA指导的RNAi有关。在这里，我们提出了一个功能模型的细胞应激，易位hAgo 2提供一个仓库功能的SG，和RNAi活性的损失之间的关系。
Various kinds of stress on human cells induce the formation of endogenous stress granules (SGs). Human Argonaute 2 (hAgo2), the catalytic core component of the RNA-induced silencing complex (RISC), can be recruited to SGs as well as P-bodies (PBs) indicating that the dynamic intracellular distribution of hAgo2 in SGs, in PBs or at other sub-cellular sites could be related to the efficiency of the RNA interference (RNAi) machinery. Here, we studied the influence of heat shock, sodium arsenite (NaAsO2), cycloheximide (CHX) and LipofectamineTM 2000-mediated transfection of phosphorothioate (PS)-modified oligonucleotides (ON) on the intracellular localization of hAgo2 and the efficiency of RNAi. Fluorescence microscopy and sedimentation analysis of cell fractions indicate stress-induced accumulation of hAgo2 in SGs and the loss of distinctly composed complexes containing hAgo2 or their sub-cellular context. Transfection of cells with PS-ON induces cell stress that is phenotypically similar to the established inducers heat shock and NaAsO2. The intracellular re-distribution of hAgo2 is related to its increased metabolic stability and to decreased RNAi directed by microRNA or by short interfering RNA. Here, we propose a functional model of the relationship between cell stress, translocation of hAgo2 to SGs providing a depot function, and loss of RNAi activity.
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DOI：
10.1073/pnas.0608845103
发表时间：
2006-11-28
影响因子：
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