Coelho Miguel B, Smith Christopher W J
Department of Biochemistry, University of Cambridge, Cambridge, UK.
Methods Mol Biol. 2014;1126:55-82. doi: 10.1007/978-1-62703-980-2_5.
Alternative splicing plays a prevalent role in generating functionally diversified proteomes from genomes with a more limited repertoire of protein-coding genes. Alternative splicing is frequently regulated with cell type or developmental specificity and in response to signaling pathways, and its mis-regulation can lead to disease. Co-regulated programs of alternative splicing involve interplay between a host of cis-acting transcript features and trans-acting RNA-binding proteins. Here, we review the current state of understanding of the logic and mechanism of regulated alternative splicing and indicate how this understanding can be exploited to manipulate splicing for therapeutic purposes.
可变剪接在从蛋白质编码基因库较为有限的基因组中产生功能多样的蛋白质组方面发挥着普遍作用。可变剪接经常受到细胞类型或发育特异性的调控,并对信号通路作出响应,其调控异常会导致疾病。可变剪接的共同调控程序涉及许多顺式作用转录特征与反式作用RNA结合蛋白之间的相互作用。在此,我们综述了目前对可变剪接调控的逻辑和机制的理解现状,并指出如何利用这一理解来操控剪接以达到治疗目的。