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Cell Discovery:中科大生科院单革实验室发现RNA干扰通路的新功能

摘要 : 近日,中国科学技术大学生命科学学院单革教授课题组在《Cell Discovery》在线发表文章:RNAi pathway participates in chromosome segregation in mammalian cells。

 近日,中国科学技术大学生命科学学院单革教授课题组在《Cell Discovery》在线发表文章:RNAi pathway participates in chromosome segregation in mammalian cells。该论文报导了在哺乳动物中RNA干扰通路在染色体分离中的功能以及功能机理。文章的第一作者是博士生黄川,单革教授为论文通讯作者。

RNA干扰通路是重要的调控细胞活动的分子机器,其主要功能是以RISC复合物通过small RNA对靶基因mRNA进行调控。然而,RNAi pathway与细胞分裂的关系,以及如何参与染色体分离研究得并不清楚。单革课题组研究发现,RNAi Pathway 核心蛋白AGO2通过由Dicer 加工的着丝粒区alpha-satellite repeat 来源的siRNA(作者命名为ASAT siRNA),特异地控制染色体上alpha-satellite transcript 非编码RNA的水平和分布,进而保证如CENPC1这样的着丝粒/动粒蛋白可以正确组装到染色体上(如下图)。该研究结果说明RNA干扰通路除了可以通过调控编码基因的mRNA来调控基因表达外,还可以通过调控哺乳动物细胞内的非编码RNA来直接调控细胞的行为。


RNAi pathway participates in chromosome segregation in mammalian cells


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.

来源: Cell Discovery 浏览次数:0


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