Exploring the Diverse Functional and Regulatory Consequences of Alternative Splicing in Development and Disease

Alternative splicing is a fundamental mechanism of eukaryotic RNA regulation that increases the transcriptomic and proteomic complexity within an organism. Moreover, alternative splicing provides a framework for generating unique yet complex tissue- and cell type-specific gene expression profiles, despite using a limited number of genes. Recent efforts to understand the negative consequences of aberrant splicing have increased our understanding of developmental and neurodegenerative diseases such as spinal muscular atrophy, frontotemporal dementia and Parkinsonism linked to chromosome 17, myotonic dystrophy, and amyotrophic lateral sclerosis. Moreover, these studies have led to the development of innovative therapeutic treatments for diseases caused by aberrant splicing, also known as spliceopathies. Despite this, a paucity of information exists on the physiological roles and specific functions of distinct transcript spliceforms for a given gene. Here, we will highlight work that has specifically explored the distinct functions of protein-coding spliceforms during development. Moreover, we will discuss the use of alternative splicing of noncoding exons to regulate the stability and localization of RNA transcripts.

Automated summary

Alternative splicing is a fundamental mechanism of eukaryotic RNA regulation that increases complexity in transcriptomes and proteomes. Understanding aberrant splicing has shed light on developmental and neurodegenerative diseases, leading to innovative therapeutic treatments. Research on distinct protein-coding spliceforms and the use of noncoding exons in alternative splicing can provide insights into physiological roles and specific functions of gene spliceforms.