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PMID: 10090730 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development.

Genes & development ·Vol. 13 ·No. 6 ·1999-03-15 ·Pages 740-53

Labourier E, Bourbon HM, Gallouzi IE, Fostier M, Allemand E, Tazi J

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.

MeSH Terms
Animals Base Sequence Binding, Competitive DNA Primers Drosophila/embryology Proteins/metabolism RNA Splicing Ribonucleoprotein, U1 Small Nuclear/metabolism
Chemicals
DNA Primers Proteins Ribonucleoprotein, U1 Small Nuclear
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Labourier E
Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique (CNRS), F34293 Montpellier Cedex 5, France.
Bourbon H M
Gallouzi I E
Fostier M
Allemand E
Tazi J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.6.740
Published
1999-03-15
Pages
740-53
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316549
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.13.6.740 PMC Full Text View journal details
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