The regulation of RNA polymerase II (pol II) transcription requires a complex and context-specific array of proteins and protein complexes, as well as nucleic acids and metabolites. Every major physiological process requires coordinated transcription of specific sets of genes at the appropriate time, and a breakdown in this regulation is a hallmark of human disease. A proliferation of recent studies has revealed that many general transcription components, including sequence-specific, DNA-binding transcription factors, Mediator, and pol II itself, are capable of liquid-liquid phase separation, to form condensates that partition these factors away from the bulk aqueous phase. These findings hold great promise for next-level understanding of pol II transcription; however, many mechanistic aspects align with more conventional models, and whether phase separation per se regulates pol II activity in cells remains controversial. In this review, we describe the conventional and condensate-dependent models, and why their similarities and differences are important. We also compare and contrast these models in the context of genome organization and pol II transcription (initiation, elongation, and termination), and highlight the central role of RNA in these processes. Finally, we discuss mutations that disrupt normal partitioning of transcription factors, and how this may contribute to disease.

RNA 聚合酶 II (pol II) 转录的调控需要一系列复杂且特定于上下文的蛋白质和蛋白质复合物，以及核酸和代谢物。每个主要的生理过程都需要在适当的时间协调转录特定的基因组，而这种调节的崩溃是人类疾病的标志。最近大量研究表明，许多一般转录成分，包括序列特异性、DNA 结合转录因子、Mediator 和 pol II 本身，都能够进行液-液相分离，形成将这些因子与转录因子分开的凝聚物。本体水相。这些发现为进一步了解 pol II 转录带来了巨大希望；然而，许多机械方面与更传统的模型一致，本身调节细胞中的 pol II 活性仍然存在争议。在这篇综述中，我们描述了传统模型和凝析油依赖模型，以及为什么它们的异同很重要。我们还在基因组组织和 pol II 转录（起始、延伸和终止）的背景下比较和对比这些模型，并强调 RNA 在这些过程中的核心作用。最后，我们讨论了破坏转录因子正常分配的突变，以及这可能如何导致疾病。