title: Regulation of alternative splicing in Drosophila by 56 RNA binding proteins.
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.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA; Broad Institute, Cambridge, Massachusetts 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
authors: Angela N
authors: AN
authors: Brooks
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Michael O
authors: MO
authors: Duff
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Gemma
authors: G
authors: May
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Li
authors: L
authors: Yang
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Mohan
authors: M
authors: Bolisetty
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Jane
authors: J
authors: Landolin
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Ken
authors: K
authors: Wan
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Jeremy
authors: J
authors: Sandler
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Benjamin W
authors: BW
authors: Booth
authors: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors: Susan E
authors: SE
authors: Celniker
authors: Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
authors: Brenton R
authors: BR
authors: Graveley
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA; Department of Plant and Microbial Biology, University of California, Berkeley, California 94720, USA.
authors: Steven E
authors: SE
authors: Brenner
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D035381:TATA-Binding Protein Associated Factors