Seifert-Davila Wolfram, van Breugel Maria Elize, van Leeuwen Fred, Müller Christoph W
Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg 69117, Germany.
Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands.
Biochem Soc Trans. 2025 Aug 29;53(4):925-934. doi: 10.1042/BST20253058.
Critical for the regulation of eukaryotic gene transcription is the assembly and interplay of general transcription factors (GTFs) with RNA polymerases (RNAPs), leading to the formation of pre-initiation complexes (PICs) as a rate-limiting step in transcription activation. Compared with RNAPII PIC assembly involving many GTFs, activators, and co-activators, RNAPIII PIC assembly is less complex, involving mainly the four GTFs TFIIIA, TFIIIB, TFIIIC, and snRNA activating protein complex with only a few additional factors. The RNAPIII-specific GTF TFIIIC is present in type I and II promoters. One prominent area of investigation has been the dynamic interaction between TFIIIC and its promoter elements, the varying affinities of TFIIIC toward these elements, and the flexible linker within TFIIIC. Additionally, evidence suggests that TFIIIC may play a dual role, acting as an assembly factor that positions TFIIIB during PIC formation and as a barrier during RNAPIII-mediated transcription. By summarizing recent structural, biochemical, and genomic data, this review explores the mechanisms by which RNAPIII-specific GTFs, with a focus on TFIIIC, dynamically regulate RNAPIII transcription.
真核基因转录调控的关键在于通用转录因子（GTF）与RNA聚合酶（RNAP）的组装及相互作用，这会导致形成前起始复合物（PIC），而这是转录激活过程中的限速步骤。与涉及众多GTF、激活因子和共激活因子的RNAPII PIC组装相比，RNAPIII PIC组装较为简单，主要涉及四个GTF，即TFIIIA、TFIIIB、TFIIIC和snRNA激活蛋白复合物，仅有少数其他因子参与。RNAPIII特异性GTF TFIIIC存在于I型和II型启动子中。一个主要的研究领域是TFIIIC与其启动子元件之间的动态相互作用、TFIIIC对这些元件的不同亲和力以及TFIIIC内的柔性连接子。此外，有证据表明TFIIIC可能发挥双重作用，在PIC形成过程中作为定位TFIIIB的组装因子，以及在RNAPIII介导的转录过程中作为屏障。通过总结近期的结构、生化和基因组数据，本综述探讨了RNAPIII特异性GTF（重点是TFIIIC）动态调节RNAPIII转录的机制。
