Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
FEBS Lett. 2018 Sep;592(17):2987-3006. doi: 10.1002/1873-3468.13119. Epub 2018 Jun 16.
Nearly all human multiexon genes are subject to alternative splicing in one or more cell types. The splicing machinery therefore has to select between multiple splice sites in a context-dependent manner, relying on sequence features in cis- and trans-acting splicing regulators that either promote or repress splice site recognition and spliceosome assembly. However, the functional coupling between multiple gene regulatory layers signifies that splicing can also be modulated by transcriptional or epigenetic characteristics. Other, less obvious, aspects of alternative splicing have come to light in recent years, often involving core components of the spliceosome previously thought to perform a basal rather than a regulatory role in splicing. Together this paints a highly dynamic picture of splicing regulation, where the final splice site choice is governed by the entire transcriptional environment of a gene and its cellular context.
几乎所有人类的多外显子基因在一种或多种细胞类型中都受到可变剪接的影响。因此，剪接机制必须在依赖于顺式和反式作用剪接调控因子的序列特征的情况下，以依赖于上下文的方式在多个剪接位点之间进行选择，这些特征促进或抑制剪接位点识别和剪接体组装。然而，多个基因调控层之间的功能偶联表明，剪接也可以被转录或表观遗传特征所调节。近年来，可变剪接的其他不太明显的方面也逐渐显现出来，这些方面通常涉及剪接体的核心组成部分，这些核心组成部分以前被认为在剪接中发挥基本而非调节作用。所有这些都描绘了一个高度动态的剪接调控图景，其中最终的剪接位点选择由基因的整个转录环境及其细胞环境决定。
