Precise regulation of gene transcription is of great importance to development and diseases. Promoter-proximal transcriptional pause is a key and general mechanism to precisely control transcription in metazoans. Subsequent to transcription initiation and synthesis of a short RNA, RNA polymerase II (Pol II) usually pauses at the promoter-proximal regions, standing by for further signals to be released into the productive elongation stage. Fine regulation of Pol II pausing and release is achieved by the concerted action of many negative and positive elongation factors, including the super elongation complex (SEC). Recent studies suggested that phase-separated assemblies of transcription regulatory complexes could provide a general biophysical basis for the dynamic regulation of transcription in response to various cellular needs, though direct evidence at endogenous level in living cells is still largely lacking. Here, we summarize and discuss latest advances in understanding how phase separation contributes to RNA polymerase II-mediated transcription, with a focus on transcriptional pause and release.

中文翻译：

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相分离、转录延伸控制和人类疾病

基因转录的精确调控对发育和疾病具有重要意义。启动子近端转录暂停是精确控制后生动物转录的关键和一般机制。在短 RNA 的转录起始和合成之后，RNA 聚合酶 II (Pol II) 通常在启动子近端区域暂停，等待进一步的信号释放到生产性延伸阶段。Pol II 暂停和释放的精细调节是通过许多负和正伸长因子的协同作用实现的，包括超伸长复合物 (SEC)。最近的研究表明，转录调控复合物的相分离组装可以为响应各种细胞需求的转录动态调控提供一般生物物理基础，尽管在很大程度上仍缺乏活细胞内源性水平的直接证据。在这里，我们总结并讨论了在理解相分离如何促进 RNA 聚合酶 II 介导的转录方面的最新进展，重点是转录暂停和释放。