CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair.
CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair.
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DOI：
10.1080/19491034.2023.2293599
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发表时间：
2023-12
期刊：
影响因子：
--
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文献类型：
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已发现非编码RNA在DNA损伤修复中发挥重要作用，而circRNA的参与尚未公开。在这里，我们表征了ciRS-7，一种含有超过70个推定的miR-7结合位点的circRNA，作为miRISC缩合和DNA修复的增强剂。体内和体外实验均证实了人miRISC的两种核心蛋白组分TNRC 6 B和AGO 2的缩合。此外，过表达ciRS-7显著增加了细胞内TNRC 6 B和AGO 2的凝聚体数量，而沉默ciRS-7则减少了其凝聚体数量，miR-7过表达也促进了miRISC的凝聚。与先前报道AGO 2参与RAD 51介导的DNA损伤修复一致，ciRS-7的过表达通过增强RAD 51募集显著促进辐射诱导的DNA损伤修复。我们的研究结果揭示了circRNA在液-液相分离中的新作用，并为ciRS-7对miRISC功能和DNA修复的调控机制提供了新的见解。
Noncoding RNAs have been found to play important roles in DNA damage repair, whereas the participation of circRNA remains undisclosed. Here, we characterized ciRS-7, a circRNA containing over 70 putative miR-7-binding sites, as an enhancer of miRISC condensation and DNA repair. Both in vivo and in vitro experiments confirmed the condensation of TNRC6B and AGO2, two core protein components of human miRISC. Moreover, overexpressing ciRS-7 largely increased the condensate number of TNRC6B and AGO2 in cells, while silencing ciRS-7 reduced it. Additionally, miR-7 overexpression also promoted miRISC condensation. Consistent with the previous report that AGO2 participated in RAD51-mediated DNA damage repair, the overexpression of ciRS-7 significantly promoted irradiation-induced DNA damage repair by enhancing RAD51 recruitment. Our results uncover a new role of circRNA in liquid-liquid phase separation and provide new insight into the regulatory mechanism of ciRS-7 on miRISC function and DNA repair.
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DOI：
10.1038/s41580-020-0264-6
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Roden C;Gladfelter AS
通讯作者：
Gladfelter AS
影响因子：
44.1
作者：
Li, Rui-Hua;Tian, Tian;Lin, Aifu
通讯作者：
Lin, Aifu
影响因子：
56.9
作者：
Giraldez, AJ;Mishima, Y;Schier, AF
通讯作者：
Schier, AF
影响因子：
64.8
作者：
Li, Pilong;Banjade, Sudeep;Cheng, Hui-Chun;Kim, Soyeon;Chen, Baoyu;Guo, Liang;Llaguno, Marc;Hollingsworth, Javoris V.;King, David S.;Banani, Salman F.;Russo, Paul S.;Jiang, Qiu-Xing;Nixon, B. Tracy;Rosen, Michael K.
通讯作者：
Rosen, Michael K.
影响因子：
64.5
作者：
Banani SF;Rice AM;Peeples WB;Lin Y;Jain S;Parker R;Rosen MK
通讯作者：
Rosen MK