A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA

Nature. 1997 Jul 24;388(6640):397-400. doi: 10.1038/41137.


Recognition of a functional 3' splice site in pre-mRNA splicing requires a heterodimer of the proteins U2AF65/U2AF35. U2AF65 binds to RNA at the polypyrimidine tract, whereas U2AF35 is thought to interact through its arginine/serine-rich (RS) domain with other RS-domain-containing factors bound at the 5' splice site, assembled in splicing enhancer complexes, or associated with the U4/U6.U5 small nuclear ribonucleoprotein complex. It is unclear, however, how such network interactions can all be established through the small RS domain in U2AF. Here we describe the function of a U2AF35-related protein (Urp), which is the human homologue of a mouse imprinted gene. Nuclear extracts depleted of Urp are defective in splicing, but activity can be restored by addition of recombinant Urp. U2AF35 could not replace Urp in complementation, indicating that their functions do not overlap. Co-immunodepletion showed that Urp is associated with the U2AF65/U2AF35 heterodimer. Binding studies revealed that Urp specifically interacts with U2AF65 through a U2AF35-homologous region and with SR proteins (a large family of RS-domain-containing proteins) through its RS domain. Therefore, Urp and U2AF35 may independently position RS-domain-containing factors within spliceosomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Genetic Complementation Test
  • HeLa Cells
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA Precursors / metabolism*
  • RNA Splicing*
  • RNA-Binding Proteins / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Ribonucleoproteins / metabolism*
  • Sequence Homology, Amino Acid
  • Splicing Factor U2AF


  • Nuclear Proteins
  • RNA Precursors
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • U2AF1 protein, human
  • U2AF2 protein, human
  • ZRSR2 protein, human
  • Zrsr1 protein, mouse
  • Zrsr2 protein, mouse

Associated data

  • GENBANK/D49677