Genetics Training Program, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
RNA Biol. 2023 Jan;20(1):525-538. doi: 10.1080/15476286.2023.2239601.
Precursor mRNA (pre-mRNA) splicing is an essential step in human gene expression and is carried out by a large macromolecular machine called the spliceosome. Given the spliceosome's role in shaping the cellular transcriptome, it is not surprising that mutations in the splicing machinery can result in a range of human diseases and disorders (spliceosomopathies). This review serves as an introduction into the main features of the pre-mRNA splicing machinery in humans and how changes in the function of its components can lead to diseases ranging from blindness to cancers. Recently, several drugs have been developed that interact directly with this machinery to change splicing outcomes at either the single gene or transcriptome-scale. We discuss the mechanism of action of several drugs that perturb splicing in unique ways. Finally, we speculate on what the future may hold in the emerging area of spliceosomopathies and spliceosome-targeted treatments.
前体信使 RNA（pre-mRNA）剪接是人类基因表达的一个基本步骤，由一个称为剪接体的大型大分子机器执行。鉴于剪接体在塑造细胞转录组中的作用，剪接机制中的突变会导致一系列人类疾病和障碍（剪接体病）也就不足为奇了。这篇综述介绍了人类 pre-mRNA 剪接机制的主要特征，以及其组成部分功能的变化如何导致从失明到癌症等各种疾病。最近，已经开发出几种直接与该机制相互作用的药物，以在单个基因或转录组水平上改变剪接结果。我们讨论了几种以独特方式扰乱剪接的药物的作用机制。最后，我们推测在新兴的剪接体病和剪接体靶向治疗领域未来可能会有哪些发展。
