RNA polymerase II clustering through carboxy-terminal domain phase separation
RNA polymerase II clustering through carboxy-terminal domain phase separation
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DOI：
10.1038/s41594-018-0112-y
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发表时间：
2018-09-01
影响因子：
16.8
通讯作者：
Zweckstetter, Markus
中科院分区：
文献类型：
--
作者：
Boehning, Marc;Dugast-Darzacq, Claire;Zweckstetter, Markus
RNA聚合酶(Pol)II的羧基末端结构域(CTD)是一个内在无序的低复杂性区域，对前mRNA的转录和加工至关重要。CTD由七个氨基酸重复组成，其数量从人类的52个到酵母的26个不等。在这里，我们报告了人和酵母CTD经过合作的液相分离，较短的酵母CTD形成不太稳定的液滴。在人类细胞中，将CTD截断为酵母CTD的长度会减少Pol II的聚集和染色质的结合，而CTD的延伸具有相反的效果。CTD液滴可以结合完整的POL II，并通过CTD与转录起始因子IIH激酶CDK7的磷酸化而溶解。结合已发表的数据，我们的结果表明，POL II通过CTD之间的相互作用和与激活剂的相互作用在活性基因上形成簇或中心，CTD磷酸化将POL II酶从中心释放出来，从而实现启动子逃逸和转录延伸。
The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is an intrinsically disordered low-complexity region that is critical for pre-mRNA transcription and processing. The CTD consists of hepta-amino acid repeats varying in number from 52 in humans to 26 in yeast. Here we report that human and yeast CTDs undergo cooperative liquid phase separation, with the shorter yeast CTD forming less-stable droplets. In human cells, truncation of the CTD to the length of the yeast CTD decreases Pol II clustering and chromatin association, whereas CTD extension has the opposite effect. CTD droplets can incorporate intact Pol II and are dissolved by CTD phosphorylation with the transcription initiation factor IIH kinase CDK7. Together with published data, our results suggest that Pol II forms clusters or hubs at active genes through interactions between CTDs and with activators and that CTD phosphorylation liberates Pol II enzymes from hubs for promoter escape and transcription elongation.