Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Institute of Biology, Westlake Institute for Advanced Study, Westlake University, Hangzhou 310064, Zhejiang Province, China.
Cold Spring Harb Perspect Biol. 2019 Jan 2;11(1):a032409. doi: 10.1101/cshperspect.a032409.
Precursor messenger RNA (pre-mRNA) splicing is executed by the spliceosome. In the past 3 years, cryoelectron microscopy (cryo-EM) structures have been elucidated for a majority of the yeast spliceosomal complexes and for a few human spliceosomes. During the splicing reaction, the dynamic spliceosome has an immobile core of about 20 protein and RNA components, which are organized around a conserved splicing active site. The divalent metal ions, coordinated by U6 small nuclear RNA (snRNA), catalyze the branching reaction and exon ligation. The spliceosome also contains a mobile but compositionally stable group of about 13 proteins and a portion of U2 snRNA, which facilitate substrate delivery into the splicing active site. The spliceosomal transitions are driven by the RNA-dependent ATPase/helicases, resulting in the recruitment and dissociation of specific splicing factors that enable the reaction. In summary, the spliceosome is a protein-directed metalloribozyme.
前体信使 RNA（pre-mRNA）剪接是由剪接体执行的。在过去的 3 年中，已经解析出大多数酵母剪接体复合物和一些人类剪接体的冷冻电镜（cryo-EM）结构。在剪接反应中，动态剪接体具有大约 20 个蛋白质和 RNA 成分的固定核心，这些成分围绕着保守的剪接活性位点组织。二价金属离子由 U6 小核 RNA（snRNA）配位，催化分支反应和外显子连接。剪接体还包含一个大约 13 个蛋白质和一部分 U2 snRNA 的可移动但组成稳定的组，它们有助于底物进入剪接活性位点。剪接体的转变由 RNA 依赖性 ATP 酶/解旋酶驱动，导致特定剪接因子的募集和解离，从而使反应能够进行。总之，剪接体是一种蛋白导向的金属核糖核酸酶。
