Identification of alternative splicing regulators by RNA interference in Drosophila
- Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301
-
Communicated by Thomas Maniatis, Harvard University, Cambridge, MA, September 21, 2004 (received for review July 29, 2004)
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.
Footnotes
-
↵ ‡ To whom correspondence should be addressed. E-mail: graveley{at}neuron.uchc.edu.
-
↵ * J.W.P. and K.P. contributed equally to this work.
-
↵ † Present address: Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261.
-
Author contributions: J.W.P., K.P., A.M.C., R.A.R., and B.R.G. designed research; J.W.P., K.P., and A.M.C. performed research; J.W.P., K.P., A.M.C., R.A.R., and B.R.G. analyzed data; and J.W.P. and B.R.G. wrote the paper.
-
Abbreviations: RNAi, RNA interference; dsRNA, double-stranded RNA; snRNP, small nuclear ribonucleoprotein.
- Copyright © 2004, The National Academy of Sciences
