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

Emmanuel Labourier, Henri Marc Bourbon, Imed Gallouzi, Maggy Fostier, Eric Allemand, Jamal Tazi

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)740-753
Number of pages14
JournalGenes and Development
Volume13
Issue number6
Publication statusPublished - 15 Mar 1999
Externally publishedYes

    Fingerprint

Keywords

  • B52/SRp55
  • pre-mRNA splicing
  • RNA-binding proteins
  • RSF1
  • SF2/ASF
  • U1 snRNP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Labourier, E., Bourbon, H. M., Gallouzi, I., Fostier, M., Allemand, E., & Tazi, J. (1999). Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development. Genes and Development, 13(6), 740-753.