title: Networking in a global world: establishing functional connections between neural splicing regulators and their target transcripts.
abstract: Recent genome-wide analyses have indicated that almost all primary transcripts from multi-exon human genes undergo alternative pre-mRNA splicing (AS). Given the prevalence of AS and its importance in expanding proteomic complexity, a major challenge that lies ahead is to determine the functional specificity of isoforms in a cellular context. A significant fraction of alternatively spliced transcripts are regulated in a tissue- or cell-type-specific manner, suggesting that these mRNA variants likely function in the generation of cellular diversity. Complementary to these observations, several tissue-specific splicing factors have been identified, and a number of methodological advances have enabled the identification of large repertoires of target transcripts regulated by these proteins. An emerging theme is that tissue-specific splicing factors regulate coherent sets of splice variants in genes known to function in related biological pathways. This review focuses on the recent progress in our understanding of neural-specific splicing factors and their regulatory networks and outlines existing and emerging strategies for uncovering important biological roles for the isoforms that comprise these networks.
authors.affiliation: Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. john.calarco@utoronto.ca
authors.forename: John A
authors.initials: JA
authors.lastname: Calarco
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D053263:Gene Regulatory Networks; D016678:Genome; D006801:Humans; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D014158:Transcription, Genetic