title: Specific interactions between proteins implicated in splice site selection and regulated alternative splicing.
abstract: Specific recognition and pairing of the 5' and 3' splice sites are critical steps in pre-mRNA splicing. We report that the splicing factors SC35 and SF2/ASF specifically interact with both the integral U1 small nuclear ribonucleoprotein (snRNP U1-70K) and with the 35 kd subunit of the splicing factor U2AF (U2AF35). Previous studies indicated that the U1 snRNP binds specifically to the 5' splice site, while U2AF35-U2AF65 heterodimer binds to the 3' splice site. Together, these observations suggest that SC35 and other members of the SR family of splicing factors may function in splice site selection by acting as a bridge between components bound to the 5' and 3' splice sites. Interestingly, SC35, SF2/ASF, and U2AF35 also interact with the Drosophila splicing regulators Transformer (Tra) and Transformer-2 (Tra2), suggesting that protein-protein interactions mediated by SR proteins may also play an important role in regulating alternative splicing.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wu
authors.forename: T
authors.initials: T
authors.lastname: Maniatis
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins; D004926:Escherichia coli / Q000378:metabolism; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009036:Moths; D009687:Nuclear Proteins / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D016601:RNA-Binding Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000378:metabolism*; D000072668:Splicing Factor U2AF; D014162:Transfection
chemical_list: D029721:Drosophila Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C066174:tra2 protein, Drosophila; D000068103:Serine-Arginine Splicing Factors