Phase separation of RNA-binding protein promotes polymerase binding and transcription.
Phase separation of RNA-binding protein promotes polymerase binding and transcription.
复制标题
RNA 结合蛋白的相分离促进聚合酶结合和转录。
DOI：
10.1038/s41589-021-00904-5
复制
发表时间：
2022
影响因子：
14.8
通讯作者：
Shen Xiaohua
中科院分区：
文献类型：
--
作者：
Shao Wen;Bi Xianju;Pan Yixuan;Gao Boyang;Wu Jun;Yin Yafei;Liu Zhimin;Peng Mengyuan;Zhang Wenhao;Jiang Xu;Ren Wenlin;Xu Yanhui;Wu Zhongyang;Wang Kaili;Zhan Ge;Lu J Yuyang;Han Xue;Li Tong;Wang Jianlong;Li Guohong;Deng Haiteng;Li Bing;Shen Xiaohua
已经提出了一个涉及RNA的转录控制相分离模型。然而，连接RNA和转录机制的分子链接仍然缺失。在这里，我们发现核糖核酸结合蛋白(RBP)构成了胚胎干细胞(ESCs)染色质蛋白质组的一半，其中一些与核糖核酸聚合酶(POL) II共定位于启动子和增强子。对典型限制性商业惯例的生化分析表明，副斑点蛋白PSPC1抑制核糖核酸诱导的POL II的提前释放，并利用核糖核酸作为多价分子促进转录缩合物的形成以及随后的磷酸化和释放POL II。这种协同作用通过PSPC1的核糖核酸结合和相分离活性增强了聚合酶的结合和活性。在ESCs中，生长素诱导的PSPC1的急性降解导致Pol II结合和新生转录的全基因组缺陷。我们认为启动子相关的RNA及其结合蛋白协同聚合酶凝聚体的相分离来促进活性转录。
An RNA-involved phase-separation model has been proposed for transcription control. However, the molecular links that connect RNA to the transcription machinery remain missing. Here we find that RNA-binding proteins (RBPs) constitute half of the chromatin proteome in embryonic stem cells (ESCs), some being colocalized with RNA polymerase (Pol) II at promoters and enhancers. Biochemical analyses of representative RBPs show that the paraspeckle protein PSPC1 inhibits the RNA-induced premature release of Pol II, and makes use of RNA as multivalent molecules to enhance the formation of transcription condensates and subsequent phosphorylation and release of Pol II. This synergistic interplay enhances polymerase engagement and activity via the RNA-binding and phase-separation activities of PSPC1. In ESCs, auxin-induced acute degradation of PSPC1 leads to genome-wide defects in Pol II binding and nascent transcription. We propose that promoter-associated RNAs and their binding proteins synergize the phase separation of polymerase condensates to promote active transcription.