Identification of alternative splicing regulators by RNA interference in <i>Drosophila</i>

Jung W. Park1, Katherine M. Parisky1, Alicia M. Celotto1, Robert A. Reenan1, Jacques Ravel1
1Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1016/S1097-2765(03)00270-3

10.1016/S0168-9525(00)02176-4

10.1146/annurev.biochem.72.121801.161720

10.1016/S0168-9525(01)02626-9

10.1016/S0968-0004(00)01604-2

10.1126/science.1090100

10.1093/genetics/159.2.599

10.1126/science.287.5461.2185

10.1083/jcb.150.2.F51

10.1083/jcb.150.2.F37

10.1016/S0092-8674(00)00049-0

10.1093/genetics/155.3.1149

10.1016/S0092-8674(00)80878-8

10.1038/35049061

10.1093/emboj/cdf668

10.1016/0092-8674(93)90316-I

10.1017/S1355838200000960

10.1038/ng1299

10.1006/dbio.2001.0429

10.1093/genetics/153.1.135

10.1126/science.1090289

10.1016/S0378-1119(98)00251-0

10.1038/35040584

10.1016/j.neuron.2004.07.020

10.1017/S1355838299991938

10.1016/S0955-0674(03)00048-6

Ruhf, M. L., Braun, A., Papoulas, O., Tamkun, J. W., Randsholt, N. & Meister, M. (2001) Development (Cambridge, U.K.) 128, 1429–1441.

10.1016/0092-8674(92)90389-T

10.1074/jbc.M212988200

10.1073/pnas.0308133100

10.1016/S1097-2765(00)80025-8

10.1126/science.1072152

10.1016/S1534-5807(03)00192-8

10.1016/S1097-2765(04)00217-5