Previous Article | Next Article 
Molecular and Cellular Biology, April 2005, p. 2969-2980, Vol. 25, No. 8
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.8.2969-2980.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
A Novel SR-Related Protein Is Required for the Second Step of Pre-mRNA Splicing
Demian Cazalla,
Kathryn Newton,
and
Javier F. Cáceres*
MRC Human Genetics Unit, Edinburgh, Scotland, United Kingdom
Received 15 November 2004/
Returned for modification 15 December 2004/
Accepted 10 January 2005
The SR family proteins and SR-related polypeptides are important regulators of pre-mRNA splicing. A novel SR-related protein of an apparent molecular mass of 53 kDa was isolated in a gene trap screen that identifies proteins which localize to the nuclear speckles. This novel protein possesses an arginine- and serine-rich domain and was termed SRrp53 (for SR-related protein of 53 kDa). In support for a role of this novel RS-containing protein in pre-mRNA splicing, we identified the mouse ortholog of the Saccharomyces cerevisiae U1 snRNP-specific protein Luc7p and the U2AF65-related factor HCC1 as interacting proteins. In addition, SRrp53 is able to interact with some members of the SR family of proteins and with U2AF35 in a yeast two-hybrid system and in cell extracts. We show that in HeLa nuclear extracts immunodepleted of SRrp53, the second step of pre-mRNA splicing is blocked, and recombinant SRrp53 is able to restore splicing activity. SRrp53 also regulates alternative splicing in a concentration-dependent manner. Taken together, these results suggest that SRrp53 is a novel SR-related protein that has a role both in constitutive and in alternative splicing.
* Corresponding author. Mailing address: MRC Human Genetics Unit, Western General Hospital, Crewe Rd., Edinburgh EH4 2XU, Scotland, United Kingdom. Phone: 44 131 467 8426. Fax: 44 131 467 8456. E-mail:
Javier.Caceres{at}hgu.mrc.ac.uk.
Present address: Virginia Mason Research Center, Seattle, WA 98101.
Molecular and Cellular Biology, April 2005, p. 2969-2980, Vol. 25, No. 8
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.8.2969-2980.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Ellis, J. D., Lleres, D., Denegri, M., Lamond, A. I., Caceres, J. F.
(2008). Spatial mapping of splicing factor complexes involved in exon and intron definition. JCB
181: 921-934
[Abstract]
[Full Text]
-
Zhou, A., Ou, A. C., Cho, A., Benz, E. J. Jr., Huang, S.-C.
(2008). Novel Splicing Factor RBM25 Modulates Bcl-x Pre-mRNA 5' Splice Site Selection. Mol. Cell. Biol.
28: 5924-5936
[Abstract]
[Full Text]
-
Howell, V. M., Jones, J. M., Bergren, S. K., Li, L., Billi, A. C., Avenarius, M. R., Meisler, M. H.
(2007). Evidence for a direct role of the disease modifier SCNM1 in splicing. Hum Mol Genet
16: 2506-2516
[Abstract]
[Full Text]
-
Puig, O., Bragado-Nilsson, E., Koski, T., Seraphin, B.
(2007). The U1 snRNP-associated factor Luc7p affects 5' splice site selection in yeast and human. Nucleic Acids Res
35: 5874-5885
[Abstract]
[Full Text]
-
Tillemans, V., Leponce, I., Rausin, G., Dispa, L., Motte, P.
(2006). Insights into Nuclear Organization in Plants as Revealed by the Dynamic Distribution of Arabidopsis SR Splicing Factors. Plant Cell
18: 3218-3234
[Abstract]
[Full Text]
-
Mangs, A. H., Speirs, H. J.L., Goy, C., Adams, D. J., Markus, M. A., Morris, B. J.
(2006). XE7: A novel splicing factor that interacts with ASF/SF2 and ZNF265. Nucleic Acids Res
34: 4976-4986
[Abstract]
[Full Text]
-
Vanhoutteghem, A., Djian, P.
(2006). Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functions. Proc. Natl. Acad. Sci. USA
103: 12423-12428
[Abstract]
[Full Text]
-
Guil, S., Long, J. C., Caceres, J. F.
(2006). hnRNP A1 Relocalization to the Stress Granules Reflects a Role in the Stress Response. Mol. Cell. Biol.
26: 5744-5758
[Abstract]
[Full Text]