Regulation of alternative splicing in Drosophila by 56 RNA binding proteins
- Angela N Brooks1,
- Michael O Duff2,
- Gemma May2,
- Li Yang2,
- Mohan Bolisetty2,
- Jane Landolin3,
- Ken Wan3,
- Jeremy Sandler3,
- Susan E Celniker3,
- Brenton R Graveley2,5 and
- Steven E Brenner4
- ↵* Corresponding author; email: graveley{at}neuron.uchc.edu
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.
- Received March 26, 2015.
- Accepted August 19, 2015.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.
