title: Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development.
abstract: Specific recognition of splice sites within metazoan mRNA precursors (pre-mRNAs) is a potential stage for gene regulation by alternative splicing. Splicing factors of the SR protein family play a major role in this regulation, as they are required for early recognition of splice sites during spliceosome assembly. Here, we describe the characterization of RSF1, a splicing repressor isolated from Drosophila, that functionally antagonizes SR proteins. Like the latter, RSF1 comprises an amino-terminal RRM-type RNA-binding domain, whereas its carboxy-terminal part is enriched in glycine (G), arginine (R), and serine (S) residues (GRS domain). RSF1 induces a dose-sensitive inhibition of splicing for several reporter pre-mRNAs, an inhibition that occurs at the level of early splicing complexes formation. RSF1 interacts, through its GRS domain, with the RS domain of the SR protein SF2/ASF and prevents the latter from cooperating with the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in binding pre-mRNA. Furthermore, overproduction of RSF 1 in the fly rescues several developmental defects caused by overexpression of the splicing activator SR protein B52/ SRp55. Therefore, RSF1 may correspond to the prototypical member of a novel family of general splicing repressors that selectively antagonize the effect of SR proteins on 5' splice-site recognition.
authors: Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique (CNRS), F34293 Montpellier Cedex 5, France.
authors: E
authors: E
authors: Labourier
authors: H M
authors: HM
authors: Bourbon
authors: I E
authors: IE
authors: Gallouzi
authors: M
authors: M
authors: Fostier
authors: E
authors: E
authors: Allemand
authors: J
authors: J
authors: Tazi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D017931:DNA Primers; D004330:Drosophila / Q000196:embryology*; D011506:Proteins / Q000378:metabolism*; D012326:RNA Splicing; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism
chemical_list: D017931:DNA Primers; D011506:Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear