Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Nat Rev Mol Cell Biol. 2017 Nov;18(11):655-670. doi: 10.1038/nrm.2017.86. Epub 2017 Sep 27.
Precursor messenger RNA (pre-mRNA) splicing is an essential step in the flow of information from DNA to protein in all eukaryotes. Research over the past four decades has molecularly delineated the splicing pathway, including characterization of the detailed splicing reaction, definition of the spliceosome and identification of its components, and biochemical analysis of the various splicing complexes and their regulation. Structural information is central to mechanistic understanding of pre-mRNA splicing by the spliceosome. X-ray crystallography of the spliceosomal components and subcomplexes is complemented by electron microscopy of the intact spliceosome. In this Review, I discuss recent atomic-resolution structures of the intact spliceosome at different stages of the splicing cycle. These structures have provided considerable mechanistic insight into pre-mRNA splicing and have corroborated and explained a large body of genetic and biochemical data. Together, the structural data have proved that the spliceosome is a protein-directed metalloribozyme.
前体信使 RNA（pre-mRNA）剪接是所有真核生物中从 DNA 到蛋白质信息流的一个基本步骤。在过去的四十年中，研究已经在分子水平上描绘了剪接途径，包括对详细剪接反应的描述、剪接体的定义及其组成部分的鉴定，以及对各种剪接复合物及其调控的生化分析。结构信息是理解剪接体进行前体 mRNA 剪接的机制的核心。剪接体成分和亚复合物的 X 射线晶体学与完整剪接体的电子显微镜互补。在这篇综述中，我讨论了不同剪接循环阶段完整剪接体的最新原子分辨率结构。这些结构为前体 mRNA 剪接提供了相当多的机制见解，并证实和解释了大量的遗传和生化数据。总的来说，结构数据证明了剪接体是一个蛋白指导的金属核糖核酸酶。
