DDX21 interacts with nuclear AGO2 and regulates the alternative splicing of SMN2
DDX21 interacts with nuclear AGO2 and regulates the alternative splicing of SMN2
复制标题
DDX21 与核 AGO2 相互作用并调节 SMN2 的选择性剪接
DOI：
10.1093/bbb/zbaa029
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发表时间：
2021-02-18
影响因子：
1.6
通讯作者：
Xiang, Shuanglin
中科院分区：
文献类型：
--
作者：
Gong, Mengting;Zhang, Xi;Xiang, Shuanglin
AGO 2是哺乳动物Ago蛋白家族中唯一具有催化活性的成员，在基因沉默中起着重要作用。近年来研究发现，包括AGO 2在内的多种基因沉默因子在细胞核中发挥作用。研究基因沉默因子在细胞核中的作用机制有助于理解基因沉默在翻译前调控基因表达中的作用。在这里，我们报告AGO 2与DDX 21间接相互作用的RNA依赖的方式，通过Co-IP和GST-下拉分析和2蛋白质目前的核灶中的免疫荧光实验。结果发现，DDX 21通过与AGO 2的间接相互作用，上调AGO 2的蛋白水平，并参与AGO 2的靶基因SNM 2的选择性剪接，产生不同表达水平的SMN 2转录本。本研究为进一步分析基因沉默组分的核功能奠定了重要的实验基础。
AGO2 is the only member of mammalian Ago protein family that possesses the catalytic activity and plays a central role in gene silencing. Recently researches reported that multiple gene silencing factors, including AGO2, function in the nuclei. The molecular mechanisms of the gene silencing factors functioning in nuclei are conducive to comprehend the roles of gene silencing in pretranslational regulation of gene expression. Here, we report that AGO2 interacts with DDX21 indirectly in an RNA-dependent manner by Co-IP and GST-Pulldown assays and the 2 proteins present nuclei foci in the immunofluorescence experiments. We found that DDX21 up-regulated the protein level of AGO2 and participated in target gene, SNM2, alternative splicing involved in AGO2 by the indirect interaction with AGO2, which produced different transcripts of SMN2 in discrepant expression level. This study laid important experiment foundation for the further analysis of the nuclear functions of gene silencing components.