Author:
Brooks Angela N.,Duff Michael O.,May Gemma,Yang Li,Bolisetty Mohan,Landolin Jane,Wan Ken,Sandler Jeremy,Booth Benjamin W.,Celniker Susan E.,Graveley Brenton R.,Brenner Steven E.
Abstract
Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.
Funder
National Science Foundation Graduate Research Fellowship
Merck Fellow of the Damon Runyon Cancer Research Foundation
National Human Genome Research Institute
Department of Energy
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics(clinical),Genetics
Cited by
73 articles.
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