Networking in a global world: Establishing functional connections between neural splicing regulators and their target transcripts
- 1Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada M5S 3E1
- 2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8
- 3Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
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.
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Reprint requests to: John A. Calarco, Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, Canada M5S 3E1; e-mail: john.calarco{at}utoronto.ca; fax: (416) 976-5545.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2603911.
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