United Kingdom Dementia Research Institute Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.
Methods Mol Biol. 2022;2537:1-19. doi: 10.1007/978-1-0716-2521-7_1.
Alternative pre-mRNA splicing allows for the production of multiple mRNAs from an individual gene, which not only expands the protein-coding potential of the genome but also enables complex mechanisms for the post-transcriptional control of gene expression. Regulation of alternative splicing entails a combinatorial interplay between an abundance of trans-acting splicing factors, cis-acting regulatory sequence elements and their concerted effects on the core splicing machinery. Given the extent and biological significance of alternative splicing in humans, it is not surprising that aberrant splicing patterns can cause or contribute to a wide range of diseases. In this introductory chapter, we outline the mechanisms that govern alternative pre-mRNA splicing and its regulation and discuss how dysregulated splicing contributes to human diseases affecting the motor system and the brain.
可变剪接使得一个基因能够产生多种 mRNA，不仅扩大了基因组的蛋白编码潜力，还为基因表达的转录后调控提供了复杂机制。可变剪接的调控涉及大量的反式作用剪接因子、顺式作用调控序列元件及其对核心剪接机制的协同作用。鉴于可变剪接在人类中的广泛程度和生物学意义，异常剪接模式会导致或促成广泛的疾病并不奇怪。在本章的引言中，我们概述了控制可变前体 mRNA 剪接及其调控的机制，并讨论了失调剪接如何导致影响运动系统和大脑的人类疾病。
