Identification of alternative splicing regulators by RNA interference in Drosophila.
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.
Park
Jung W
JW
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301, USA.
Parisky
Katherine
K
Celotto
Alicia M
AM
Reenan
Robert A
RA
Graveley
Brenton R
BR
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
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D016601:RNA-Binding Proteins