Alternative Splicing in the Mammalian Nervous System: Recent Insights into Mechanisms and Functional Roles

High-throughput transcriptomic profiling approaches have revealed that alternative splicing (AS) of precursor mRNAs, a fundamental process by which cells expand their transcriptomic diversity, is particularly widespread in the nervous system. AS events detected in the brain are more highly conserved than those detected in other tissues, suggesting that they more often provide conserved functions. Our understanding of the mechanisms and functions of neural AS events has significantly advanced with the coupling of various computational and experimental approaches. These studies indicate that dynamic regulation of AS in the nervous system is critical for modulating protein-protein interactions, transcription networks, and multiple aspects of neuronal development. Furthermore, several underappreciated classes of AS with the aforementioned roles in neuronal cells have emerged from unbiased, global approaches. Collectively, these findings emphasize the importance of characterizing neural AS in order to gain new insight into pathways that may be altered in neurological diseases and disorders. Alternative splicing generates vast isoform diversity in the nervous system. Raj and Blencowe review how high-throughput profiling, computational approaches, animal models, and biochemical methods have provided remarkable new insights into the complexity and function of the neural-regulated alternative splicing landscape.