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Molecular and Cellular Biology, February 2004, p. 1174-1187, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1174-1187.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human RNPS1 and Its Associated Factors: a Versatile Alternative Pre-mRNA Splicing Regulator In Vivo

Eiji Sakashita,^1,2 Sawako Tatsumi,^1, Dieter Werner,³ Hitoshi Endo,² and Akila Mayeda^1*

Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33136-1019,¹ Department of Biochemistry, Jichi Medical School, Tochigi 329-0498, Japan,² Division of Biochemistry of the Cell, German Cancer Research Center, Heidelberg D-69120, Germany³

Received 27 June 2003/ Returned for modification 12 August 2003/ Accepted 29 October 2003

Human RNPS1 was originally purified and characterized as a pre-mRNA splicing activator, and its role in the postsplicing process has also been proposed recently. To search for factors that functionally interact with RNPS1, we performed a yeast two-hybrid screen with a human cDNA library. Four factors were identified: p54 (also called SRp54; a member of the SR protein family), human transformer 2ß (hTra2ß; an exonic splicing enhancer-binding protein), hLucA (a potential component of U1 snRNP), and pinin (also called DRS and MemA; a protein localized in nuclear speckles). The N-terminal region containing the serine-rich (S) domain, the central RNA recognition motif (RRM), and the C-terminal arginine/serine/proline-rich (RS/P) domain of RNPS1 interact with p54, pinin, and hTra2ß, respectively. Protein-protein binding between RNPS1 and these factors was verified in vitro and in vivo. Overexpression of RNPS1 in HeLa cells induced exon skipping in a model ß-globin pre-mRNA and a human tra-2ß pre-mRNA. Coexpression of RNPS1 with p54 cooperatively stimulated exon inclusion in an ATP synthase -subunit pre-mRNA. The RS/P domain and RRM are necessary for the exon-skipping activity, whereas the S domain is important for the cooperative effect with p54. RNPS1 appears to be a versatile factor that regulates alternative splicing of a variety of pre-mRNAs.

Present address: Department of Geriatric Research, National Institute for Longevity Sciences, Aichi 474-8522, Japan.

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