Cell-type-specific gene expression is a fundamental feature of multicellular organisms and is achieved by combinations of regulatory strategies. Although cell-restricted transcription is perhaps the most widely studied mechanism, co-transcriptional and post-transcriptional processes are also central to the spatiotemporal control of gene functions. One general category of expression control involves the generation of multiple transcript isoforms from an individual gene, whose balance and cell specificity are frequently tightly regulated via diverse strategies. The nervous system makes particularly extensive use of cell-specific isoforms, specializing the neural function of genes that are expressed more broadly. Here, we review regulatory strategies and RNA-binding proteins that direct neural-specific isoform processing. These include various classes of alternative splicing and alternative polyadenylation events, both of which broadly diversify the neural transcriptome. Importantly, global alterations of splicing and alternative polyadenylation are characteristic of many neural pathologies, and recent genetic studies demonstrate how misregulation of individual neural isoforms can directly cause mutant phenotypes.
© 2023 Lee et al.