Department of Cell Biology, Blavatnik Institute, Harvard Medical School, 240 Longwood Ave., Boston, MA, 02115, USA. Electronic address: https://twitter.com/@LucasFarnung.
Massachusetts Institute of Technology, Department of Biology, 31 Ames St., Cambridge, MA, 02142, USA.
Curr Opin Struct Biol. 2022 Apr;73:102335. doi: 10.1016/j.sbi.2022.102335. Epub 2022 Feb 17.
The first step of eukaryotic gene expression is the assembly of RNA polymerase II and general transcription factors on promoter DNA. This highly regulated process involves ∼80 different proteins that together form the preinitiation complex (PIC). Decades of work have gone into understanding PIC assembly using biochemical and structural approaches. These efforts have yielded significant but partial descriptions of PIC assembly. Over the past few years, cryo-electron microscopy has provided the first high-resolution structures of the near-complete mammalian PIC assembly. These structures have revealed that PIC assembly is a highly dynamic process. This review will summarize recent structural findings and discuss their implications for understanding cell type-specific gene expression.
真核基因表达的第一步是 RNA 聚合酶 II 和一般转录因子在启动子 DNA 上的组装。这个高度调控的过程涉及到约 80 种不同的蛋白质,它们共同组成了起始前复合物 (PIC)。几十年来,人们一直致力于使用生化和结构方法来理解 PIC 的组装。这些努力已经对 PIC 组装进行了重要但不完整的描述。在过去的几年中,冷冻电子显微镜为近完整的哺乳动物 PIC 组装提供了第一个高分辨率结构。这些结构揭示了 PIC 组装是一个高度动态的过程。这篇综述将总结最近的结构发现,并讨论它们对理解细胞类型特异性基因表达的意义。