Activation of pre-mRNA splicing by human RNPS1 is regulated by CK2 phosphorylation

Janeen H. Trembley, Sawako Tatsumi, Eiji Sakashita, Pascal Loyer, Clive A. Slaughter, Hitoshi Suzuki, Hitoshi Endo, Vincent J. Kidd, Akila Mayeda

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Human RNPS1 was originally characterized as a pre-mRNA splicing activator in vitro and was shown to regulate alternative splicing in vivo. RNPS1 was also identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and a role for RNPS1 in postsplicing processes has been proposed. Here we demonstrate that RNPS1 incorporates into active spliceosomes, enhances the formation of the ATP-dependent A complex, and promotes the generation of both intermediate and final spliced products. RNPS1 is phosphorylated in vivo and interacts with the CK2 (casein kinase II) protein kinase. Serine 53 (Ser-53) of RNPS1 was identified as the major phosphorylation site for CK2 in vitro, and the same site is also phosphorylated in vivo. The phosphorylation status of Ser-53 significantly affects splicing activation in vitro, but it does not perturb the nuclear localization of RNPS1. In vivo experiments indicated that the phosphorylation of RNPS1 at Ser-53 influences the efficiencies of both splicing and translation. We propose that RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 phosphorylation.

Original languageEnglish (US)
Pages (from-to)1446-1457
Number of pages12
JournalMolecular and Cellular Biology
Volume25
Issue number4
DOIs
Publication statusPublished - Feb 1 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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