美国约翰霍普金斯大学Carl Wu团队发现，无序C端结构域驱动RNAPII的时空限制来加强对染色质靶标的搜索。相关论文于2024年3月28日在线发表在《自然—细胞生物学》杂志上。

研究人员表示，高效的基因表达需要RNA聚合酶II（RNAPII）在空间和时间上精确地找到染色质靶标。RNAPII如何在三维核空间中进行这种复杂的扩散式搜索，在很大程度上仍是未知数。RNAPII的无序羧基末端结构域（CTD）对招募转录相关蛋白至关重要，它在体外形成相分离的液滴，暗示了它在调节RNAPII动态中的潜在作用。

研究人员在活体酵母中使用单分子追踪和时空映射技术，证明CTD是限制RNAPII在富含活性基因的亚核区域内扩散所必需的，但并没有明显的相分离凝集。维持RNAPII限制需要中介体和全局性染色质组织。值得注意的是，截断CTD会破坏RNAPII的空间限制、延长靶标搜索时间、减少染色质结合、损害启动前复合物的形成并降低转录爆发。这项研究揭示了CTD驱动RNAPII时空限制以实现高效基因表达的关键作用。

附：英文原文

Title: Disordered C-terminal domain drives spatiotemporal confinement of RNAPII to enhance search for chromatin targets

Author: Ling, Yick Hin, Ye, Ziyang, Liang, Chloe, Yu, Chuofan, Park, Giho, Corden, Jeffry L., Wu, Carl

Issue&Volume: 2024-03-28

Abstract: Efficient gene expression requires RNA polymerase II (RNAPII) to find chromatin targets precisely in space and time. How RNAPII manages this complex diffusive search in three-dimensional nuclear space remains largely unknown. The disordered carboxy-terminal domain (CTD) of RNAPII, which is essential for recruiting transcription-associated proteins, forms phase-separated droplets in vitro, hinting at a potential role in modulating RNAPII dynamics. In the present study, we use single-molecule tracking and spatiotemporal mapping in living yeast to show that the CTD is required for confining RNAPII diffusion within a subnuclear region enriched for active genes, but without apparent phase separation into condensates. Both Mediator and global chromatin organization are required for sustaining RNAPII confinement. Remarkably, truncating the CTD disrupts RNAPII spatial confinement, prolongs target search, diminishes chromatin binding, impairs pre-initiation complex formation and reduces transcription bursting. The present study illuminates the pivotal role of the CTD in driving spatiotemporal confinement of RNAPII for efficient gene expression.

DOI: 10.1038/s41556-024-01382-2

Source: https://www.nature.com/articles/s41556-024-01382-2