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Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing.

Previous studies have shown that protein-protein interactions among splicing factors may play an important role in pre-mRNA splicing. We report here identification and functional characterization of a new splicing factor, Sip1 (SC35-interacting protein 1). Sip1 was initially identified by virtue of its interaction with SC35, a splicing factor of the SR family. Sip1 interacts with not only several SR proteins but also with U1-70K and U2AF65, proteins associated with 5' and 3' splice sites, respectively. The predicted Sip1 sequence contains an arginine-serine-rich (RS) domain but does not have any known RNA-binding motifs, indicating that it is not a member of the SR family. Sip1 also contains a region with weak sequence similarity to the Drosophila splicing regulator suppressor of white apricot (SWAP). An essential role for Sip1 in pre-mRNA splicing was suggested by the observation that anti-Sip1 antibodies depleted splicing activity from HeLa nuclear extract. Purified recombinant Sip1 protein, but not other RS domain-containing proteins such as SC35, ASF/SF2, and U2AF65, restored the splicing activity of the Sip1-immunodepleted extract. Addition of U2AF65 protein further enhanced the splicing reconstitution by the Sip1 protein. Deficiency in the formation of both A and B splicing complexes in the Sip1-depleted nuclear extract indicates an important role of Sip1 in spliceosome assembly. Together, these results demonstrate that Sip1 is a novel RS domain-containing protein required for pre-mRNA splicing and that the functional role of Sip1 in splicing is distinct from those of known RS domain-containing splicing factors.

Pubmed ID: 9447963


  • Zhang WJ
  • Wu JY


Molecular and cellular biology

Publication Data

February 24, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA114197
  • Agency: NCI NIH HHS, Id: R01 CA114197-01A2
  • Agency: NEI NIH HHS, Id: R01 EY014576
  • Agency: NEI NIH HHS, Id: R01 EY014576-03
  • Agency: NIGMS NIH HHS, Id: R01 GM070967
  • Agency: NIGMS NIH HHS, Id: R01 GM070967-02
  • Agency: NIGMS NIH HHS, Id: R01 GM53945

Mesh Terms

  • Amino Acid Sequence
  • Fungal Proteins
  • HeLa Cells
  • Humans
  • Immune Sera
  • Molecular Sequence Data
  • Nuclear Proteins
  • RNA Precursors
  • RNA Splicing
  • Recombinant Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • Ribonucleoproteins
  • Spliceosomes