Department of Structural Biology, Genentech Inc., South San Francisco, California 94080, USA
RNA. 2024 Oct 16;30(11):1397-1407. doi: 10.1261/rna.080198.124.
The spliceosome is a eukaryotic multimegadalton RNA-protein complex that removes introns from transcripts. The spliceosome ensures the selection of each exon-intron boundary through multiple recognition events. Initially, the 5' splice site (5' SS) and branch site (BS) are bound by the U1 small nuclear ribonucleoprotein (snRNP) and the U2 snRNP, respectively, while the 3' SS is mostly determined by proximity to the branch site. A large number of splicing factors recognize the splice sites and recruit the snRNPs before the stable binding of the snRNPs occurs by base-pairing the snRNA to the transcript. Fidelity of this process is crucial, as mutations in splicing factors and U2 snRNP components are associated with many diseases. In recent years, major advances have been made in understanding how splice sites are selected in and humans. Here, I review and discuss the current understanding of the recognition of splice sites by the spliceosome with a focus on recognition and binding of the branch site by the U2 snRNP in humans.
剪接体是一种真核多亚基 RNA-蛋白复合物，可从转录本中切除内含子。剪接体通过多种识别事件确保每个外显子-内含子边界的选择。最初，5'剪接位点（5' SS）和分支位点（BS）分别由 U1 小核核糖核蛋白（snRNP）和 U2 snRNP 结合，而 3' SS 主要由与分支位点的接近程度决定。大量剪接因子识别剪接位点，并在 snRNP 通过与转录本的碱基配对稳定结合之前募集 snRNP。这个过程的保真度至关重要，因为剪接因子和 U2 snRNP 成分的突变与许多疾病有关。近年来，人们在理解剪接体如何选择和人类的剪接位点方面取得了重大进展。在这里，我回顾和讨论了剪接体识别剪接位点的当前理解，重点是人类 U2 snRNP 对分支位点的识别和结合。
