Alternative Splicing in Human Biology and Disease

Abstract

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.

Keywords: Alternative splicing; Amyotrophic lateral sclerosis; Cis-acting regulatory elements; Frontotemporal dementia with parkinsonism linked to chromosome 17; Myotonic dystrophy type 1; Spinal muscular atrophy; Trans-acting splicing factors; snRNPs.