Nagel Michael, Taatjes Dylan J
Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA.
Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA.
Mol Cell. 2025 May 15;85(10):1907-1919. doi: 10.1016/j.molcel.2025.04.011.
The regulation of RNA polymerase II (RNAPII) activity requires orchestrated responses among genomic regulatory sequences and an expansive set of proteins and protein complexes. Despite intense study over five decades, mechanistic insights continue to emerge. Within the past 10 years, live-cell imaging and single-cell transcriptomics experiments have yielded new information about enhancer-promoter communication, transcription factor dynamics, and the kinetics of RNAPII transcription activation. These insights have established RNAPII re-initiation and bursting as a common regulatory phenomenon with widespread implications for gene regulation in health and disease. Here, we summarize regulatory strategies that help control RNAPII bursting in eukaryotic cells, which is defined as short periods of active transcription followed by longer periods of inactivity. We focus on RNAPII re-initiation (i.e., a "burst" of two or more polymerases that initiate from the same promoter), with an emphasis on molecular mechanisms, open questions, and controversies surrounding this distinct regulatory stage.
RNA聚合酶II(RNAPII)活性的调控需要基因组调控序列与大量蛋白质及蛋白质复合物之间协调一致的反应。尽管历经五十多年的深入研究,但对其机制的认识仍在不断涌现。在过去十年中,活细胞成像和单细胞转录组学实验产生了关于增强子-启动子通讯、转录因子动态以及RNAPII转录激活动力学的新信息。这些认识已将RNAPII重新起始和转录爆发确立为一种普遍的调控现象,对健康和疾病中的基因调控具有广泛影响。在这里,我们总结了有助于控制真核细胞中RNAPII转录爆发的调控策略,转录爆发被定义为活跃转录的短时期后接着是较长时间的不活跃期。我们专注于RNAPII重新起始(即从同一启动子起始的两个或更多聚合酶的“爆发”),重点关注围绕这一独特调控阶段的分子机制、未解决的问题和争议。
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