RNAi pathway participates in chromosome segregation in mammalian cells.
RNAi pathway participates in chromosome segregation in mammalian cells.
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RNAi 途径参与哺乳动物细胞中的染色体分离。
DOI：
10.1038/celldisc.2015.29
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发表时间：
2015
期刊：
影响因子：
33.5
通讯作者：
Shan G
中科院分区：
文献类型：
--
作者：
Huang C;Wang X;Liu X;Cao S;Shan G
RNAi机制是无数生命事件中的强大调节器。尽管有证据表明小RNA和RNAi途径的组分可能与不同生物体中有丝分裂染色体的结构和行为相关，但RNAi途径在哺乳动物有丝分裂染色体分离中的直接作用仍然难以捉摸。在这里，我们报告Dicer和AGO 2，哺乳动物RNAi途径的两个核心组件，参与染色体分离。Dicer或AGO 2的敲除导致染色体滞后的发生率更高，并且这种效应不依赖于用DGCR 8敲除细胞检查的microRNA。进一步的研究表明，α-卫星RNA（α-satellite RNA，α-satellite RNA）是一种来源于着丝粒重复区的非编码RNA，在Dicer产生的内源性小干扰RNA（ASAT siRNA）的指导下，由AGO 2调控。此外，AGO 2的切割活性是染色体分离所必需的。染色体相关α-卫星RNA的水平和分布对着丝粒蛋白如着丝粒蛋白C1（centromere protein C1，CENPC 1）的定位具有重要的调控作用。通过这些结果，我们还提供了一个范例，其中RNAi途径通过维持细胞中非编码RNA的水平和分布参与重要的细胞事件。
The RNAi machinery is a mighty regulator in a myriad of life events. Despite lines of evidence that small RNAs and components of the RNAi pathway may be associated with structure and behavior of mitotic chromosomes in diverse organisms, a direct role of the RNAi pathway in mammalian mitotic chromosome segregation remains elusive. Here we report that Dicer and AGO2, two central components of the mammalian RNAi pathway, participate in the chromosome segregation. Knockdown of Dicer or AGO2 results in a higher incidence of chromosome lagging, and this effect is independent from microRNAs as examined with DGCR8 knockout cells. Further investigation has revealed that α-satellite RNA, a noncoding RNA derived from centromeric repeat region, is managed by AGO2 under the guidance of endogenous small interference RNAs (ASAT siRNAs) generated by Dicer. Furthermore, the slicer activity of AGO2 is essential for the chromosome segregation. Level and distribution of chromosome-associated α-satellite RNA have crucial regulatory effect on the localization of centromeric proteins such as centromere protein C1 (CENPC1). With these results, we also provide a paradigm in which the RNAi pathway participates in vital cellular events through the maintenance of level and distribution of noncoding RNAs in cells.