Serine-Arginine (SR) Protein-like Factors That Antagonize Authentic SR Proteins and Regulate Alternative Splicing

Alison E. Cowper, Javier F. Cáceres, Akira Maeda, Gavin R. Screaton

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We have characterized two RNA-binding proteins, of apparent molecular masses of ∼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 ribonucleo-protein 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 ∼40 and ∼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.

Original languageEnglish
Pages (from-to)48908-48914
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number52
DOIs
Publication statusPublished - 28-12-2001

Fingerprint

Alternative Splicing
Serine
Arginine
RNA Splice Sites
Proteins
Dipeptides
RNA
Recombinant Fusion Proteins
Repressor Proteins
RNA-Binding Proteins
RNA Precursors
Thromboplastin
Nuclear Proteins
Cell Extracts
HeLa Cells
Adenoviridae
Molecular mass
Complement System Proteins
Modulation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cowper, Alison E. ; Cáceres, Javier F. ; Maeda, Akira ; Screaton, Gavin R. / Serine-Arginine (SR) Protein-like Factors That Antagonize Authentic SR Proteins and Regulate Alternative Splicing. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 52. pp. 48908-48914.
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Serine-Arginine (SR) Protein-like Factors That Antagonize Authentic SR Proteins and Regulate Alternative Splicing. / Cowper, Alison E.; Cáceres, Javier F.; Maeda, Akira; Screaton, Gavin R.

In: Journal of Biological Chemistry, Vol. 276, No. 52, 28.12.2001, p. 48908-48914.

Research output: Contribution to journalArticle

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