Serine-arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing

J Biol Chem. 2001 Dec 28;276(52):48908-14. doi: 10.1074/jbc.M103967200. Epub 2001 Oct 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Active Transport, Cell Nucleus
  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Animals
  • Cell Cycle Proteins
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Mice
  • Molecular Sequence Data
  • Molecular Weight
  • Neoplasm Proteins*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Serine-Arginine Splicing Factors
  • Tissue Distribution


  • Cell Cycle Proteins
  • Fusip1 protein, mouse
  • Neoplasm Proteins
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SRSF10 protein, human
  • SRSF12 protein, human
  • Serine-Arginine Splicing Factors

Associated data

  • GENBANK/AF449427
  • GENBANK/AF449428