Phase separation of RNA-binding protein promotes polymerase binding and transcription

• Published in: Nature chemical biology Vol. 18; no. 1; pp. 70 - 80
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2022; Nature Publishing Group
• Subjects: 631/337/572; 631/92/500; 631/92/612/1230; Biochemical Engineering; Biochemistry; Bioorganic Chemistry; Cell Biology; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Chromatin; Condensates; DNA-directed RNA polymerase; Embryo cells; Enhancers; Gene Expression Regulation; Genomes; Phase separation; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Proteins; Proteomes; RNA polymerase; RNA Polymerase II - metabolism; RNA-binding protein; RNA-Binding Proteins - metabolism; Stem cells; Synergism; Transcription; Transcription, Genetic
• ISSN: 1552-4450; 1552-4469
• DOI: 10.1038/s41589-021-00904-5

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. With the example of the paraspeckle protein PSPC1, Shao et al. demonstrated the synergistic interplay of promoter-associated RNA and its binding proteins in promoting transcription condensate formation and Pol II engagement and activity via phase separation.