title: Serine-arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing.
abstract: We have characterized two RNA-binding proteins, of apparent molecular masses of approximately 40 and 35 kDa, which possess a single N-terminal RNA-recognition motif (RRM) followed by a C-terminal domain rich in serine-arginine dipeptides. Their primary structures resemble the single-RRM serine-arginine (SR) protein, SC35; however their functional effects are quite distinctive. The 40-kDa protein cannot complement SR protein-deficient HeLa cell S100 extract and showed a dominant negative effect in vitro against the authentic SR proteins, SF2/ASF and SC35. Interestingly, the 40- and 35-kDa proteins antagonize SR proteins and activate the most distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo, an activity that is similar to that characterized previously for the heterogeneous nuclear ribonucleoprotein particles A/B group of proteins. A series of recombinant chimeric proteins consisting of domains from these proteins and SC35 in various combinations showed that the RRM, but not the C-terminal domain rich in serine-arginine dipeptides, has a dominant role in this activity. Because of the similarity to SR proteins we have named these proteins SRrp40 and SRrp35, respectively, for SR-repressor proteins of approximately 40 and approximately 35 kDa. Both factors show tissue- and cell type-specific patterns of expression. We propose that these two proteins are SR protein-like alternative splicing regulators that antagonize authentic SR proteins in the modulation of alternative 5' splice site choice.
authors.affiliation: Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
authors.forename: A E
authors.initials: AE
authors.lastname: Cowper
authors.forename: J F
authors.initials: JF
authors.lastname: Cáceres
authors.forename: A
authors.initials: A
authors.lastname: Mayeda
authors.forename: G R
authors.initials: GR
authors.lastname: Screaton
mesh_terms: D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000068103:Serine-Arginine Splicing Factors; D014018:Tissue Distribution
chemical_list: D018797:Cell Cycle Proteins; C485446:Fusip1 protein, mouse; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C115188:SRSF10 protein, human; C445312:SRSF12 protein, human; D000068103:Serine-Arginine Splicing Factors