Integrative Modeling Defines the Nova Splicing-Regulatory Network and Its Combinatorial Controls

Abstract

Making the Final Cut RNA splicing, which involves selectively cutting and pasting messenger RNA to generate different proteins, is critical in regulating human physiology and diseases. However, our knowledge of the underlying rules governing splicing regulation remains incomplete. The recent emergence of next-generation sequencing and other high-throughput technologies has provided an opportunity to transform our understanding of RNA regulation. Zhang et al. (p. 439 , published online 17 June) combined multiple data sets to generate a robust and relatively complete picture of splicing regulation by the mammalian neuronal splicing factor Nova in the brain. About 700 splicing events were identified, including many novel target exons, some likely to be involved in neurological disease. Combining genomic studies with computational biology also yielded insight into the regulation of alternative splicing.