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

AUTOR(ES)

Labourier, Emmanuel

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

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.

Documentos Relacionados

• Initial recognition of U12-dependent introns requires both U11/5′ splice-site and U12/branchpoint interactions
• Ordered Partitioning Reveals Extended Splice-Site Consensus Information
• A Second Leaky Splice-Site Mutation in the Spastin Gene
• Genes of nuclear encoded mitochondrial proteins: evidence for a variant of the 3' splice-site consensus sequence.
• Suppression of mammalian 5' splice-site defects by U1 small nuclear RNAs from a distance.