title: Identification of alternative splicing regulators by RNA interference in Drosophila.
abstract: Alternative splicing is thought to be regulated by nonspliceosomal RNA binding proteins that modulate the association of core components of the spliceosome with the pre-mRNA. Although the majority of metazoan genes encode pre-mRNAs that are alternatively spliced, remarkably few splicing regulators are currently known. Here, we used RNA interference to examine the role of >70% of the Drosophila RNA-binding proteins in regulating alternative splicing. We identified 47 proteins as splicing regulators, 26 of which have not previously been implicated in alternative splicing. Many of the regulators we identified are nonspliceosomal RNA-binding proteins. However, our screen unexpectedly revealed that altering the concentration of certain core components of the spliceosome specifically modulates alternative splicing. These results significantly expand the number of known splicing regulators and reveal an extraordinary richness in the mechanisms that regulate alternative splicing.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301, USA.
authors.forename: Jung W
authors.initials: JW
authors.lastname: Park
authors.forename: Katherine
authors.initials: K
authors.lastname: Parisky
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Celotto
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reenan
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015815:Cell Adhesion Molecules; D002467:Cell Nucleus / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D017344:Genes, Insect; D009154:Mutation; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D016601:RNA-Binding Proteins