RT Journal
A1 Brooks, Angela N.
A1 Duff, Michael O.
A1 May, Gemma
A1 Yang, Li
A1 Bolisetty, Mohan
A1 Landolin, Jane
A1 Wan, Ken
A1 Sandler, Jeremy
A1 Booth, Benjamin W.
A1 Celniker, Susan E.
A1 Graveley, Brenton R.
A1 Brenner, Steven E.
T1 Regulation of alternative splicing in Drosophila by 56 RNA binding proteins
JF Genome Research 
JO Genome Research 
YR 2015 
FD November 01 
VO 25 
IS 11 
SP 1771 
OP 1780 
DO 10.1101/gr.192518.115 
UL http://genome.cshlp.org/content/25/11/1771.abstract 
AB 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.