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.

已经提出了一种涉及 RNA 的相分离模型用于转录控制。然而，将 RNA 连接到转录机制的分子链仍然缺失。在这里，我们发现 RNA 结合蛋白 (RBP) 构成了胚胎干细胞 (ESC) 染色质蛋白质组的一半，其中一些在启动子和增强子处与 RNA 聚合酶 (Pol) II 共定位。代表性 RBP 的生化分析表明，副啄木鸟蛋白 PSPC1 抑制 RNA 诱导的 Pol II 过早释放，并利用 RNA 作为多价分子来增强转录凝聚物的形成以及随后的 Pol II 磷酸化和释放。这种协同相互作用通过 PSPC1 的 RNA 结合和相分离活性增强了聚合酶的参与和活性。在 ESC 中，生长素诱导的 PSPC1 急性降解导致 Pol II 结合和新生转录的全基因组缺陷。我们建议启动子相关 RNA 及其结合蛋白协同聚合酶缩合物的相分离以促进活性转录。