Abstract
SR (serine-arginine) proteins are essential pre-mRNA splicing factors. Several SR proteins have been characterized in humans, among them SR-A1. It has been demonstrated by members of our group that the SR-A1 gene is constitutively expressed in most of the human tissues, while its transcription is increased in breast carcinoma cell lines. Moreover, the SR-A1 gene is overexpressed in a set of ovarian tumors, suggesting that it may be involved in the pathogenesis and/or progression of ovarian cancer. Therefore, in the present study we examined the expression of the SR-A1 gene in colon cancer tissues by RT-PCR and found that it is overexpressed as compared to normal mucosa (p=0.01). The SR-A1 gene was expressed more frequently in well-differentiated tumors than those with poor differentiation. Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that SR-A1-positivity is associated with a long survival (p=0.044). However, when entered into a Cox multivariate model adjusted for other clinicopathological features studied, SR-A1 expression status was not found to be of independent prognostic significance. To the best of our knowledge, this is the first study examining the expression of the novel gene SR-A1 in colon cancer progression.
References
Birney, E., Kumar, S. and Krainer, A.R. (1993). Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res.21, 5803–5816.10.1093/nar/21.25.5803Search in Google Scholar
Black, D.L. (2003). Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem.72, 291–336.10.1146/annurev.biochem.72.121801.161720Search in Google Scholar
Blencowe, B.J., Nickerson, J.A., Issner, R., Peunman, S. and Sharp, P.A. (1994). Association of nuclear matrix antigens with exon-counting splicing complexes. J. Cell Biol.127, 593–607.10.1083/jcb.127.3.593Search in Google Scholar
Blencowe, B.J., Issner, R., Nickerson, J.A., Sharp, P.A. (1998). A coactivator of pre-mRNA splicing. Genes Dev.12, 996–1009.10.1101/gad.12.7.996Search in Google Scholar
Blencowe, B.J. (2000). Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem. Sci.25, 106–110.10.1016/S0968-0004(00)01549-8Search in Google Scholar
Caceres, J.F. and Krainer, A.R. (1997). Mammalian pre-mRNA splicing factors. In: Eukaryotic mRNA Processing, A.R. Krainer, ed. (New York, USA: Oxford University Press), pp. 174–212.Search in Google Scholar
Caceres, J.F., Misteli, T., Screaton, G.R., Spector, D.L. and Krainer, A.R. (1997). Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity. J. Cell Biol.138, 225–238.10.1083/jcb.138.2.225Search in Google Scholar PubMed PubMed Central
Cavaloc, Y., Popielarz, M., Fuchs, J.P., Gattoni, R. and Stevenin, J. (1994). Characterization and cloning of the human splicing factor 9G8: a novel 35 kDa factor of the serine/arginine protein family. EMBO J.13, 2639–2649.10.1002/j.1460-2075.1994.tb06554.xSearch in Google Scholar PubMed PubMed Central
Chew, S.L., Liu, H.-X., Mayeda, A. and Krainer, A.R. (1999). Evidence for the function of an exonic splicing enhancer after the first catalytic step of pre-mRNA splicing. Proc. Natl. Acad. Sci. USA96, 10655–10660.10.1073/pnas.96.19.10655Search in Google Scholar PubMed PubMed Central
Faustino, N.A., and Cooper, T.A. (2003). Pre-mRNA splicing and human disease. Genes Dev.17, 419–437.10.1101/gad.1048803Search in Google Scholar PubMed
Fu, X.D. and Maniatis, T. (1992). Isolation of a complementary DNA that encodes the mammalian splicing factor SC35. Science256, 535–538.10.1126/science.1373910Search in Google Scholar PubMed
Ge, H., Zuo, P. and Manley, J.L. (1991). Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators. Cell66, 373–382.10.1016/0092-8674(91)90626-ASearch in Google Scholar
Ghigna, C., Moroni, M., Porta, C., Riva, S. and Biamonti, G. (1998). Altered expression of heterogeneous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas. Cancer Res.58, 5818–5824.Search in Google Scholar
Gobert, C., Bracco, L., Rossi, F., Olivier, M., Tazi, J., Lavelle, F., Larsen, A.K. and Riou, J.F. (1996). Modulation of DNA topoisomerase I activity by p53. Biochemistry35, 5778–5786.10.1021/bi952327wSearch in Google Scholar
Jamison, S.F., Pasman, Z., Wang, J., Will, C., Luhrmann, R., Manley, J.L. and Garcia-Blanco, M.A. (1995). U1 snRNP-ASF/SF2 interaction and 5′ splice site recognition: characterization of required elements. Nucleic Acids Res.23, 3260–3267.10.1093/nar/23.16.3260Search in Google Scholar
Kim, Y.J., Zuo, P., Manley, J.L. and Baker, B.S. (1992). Drosophila RNA-binding protein RBP1 is localized to transcriptionally active sites of chromosomes and shows a functional similarity to human splicing factor ASF/SF2. Genes Dev.6, 2569–2579.10.1101/gad.6.12b.2569Search in Google Scholar
Krainer, A.R. (1996). The structure and function of proteins involved in mammalian pre-mRNA splicing. Annu. Rev. Biochem.65, 367–409.10.1146/annurev.bi.65.070196.002055Search in Google Scholar
Liu, L., Lin, J.J., Chen, X., Liu, X. and Xu, P. (2003). Neural expression and regulation of NSSP1 proteins. Neuroreport14, 1847–1850.10.1097/00001756-200310060-00018Search in Google Scholar
Mathioudaki, K., Scorilas, A., Papadokostopoulou, A., Xynopoulos, D., Arnogiannaki, N., Agnanti, N. and Talieri, M. (2004). Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer. Biol. Chem.385, 779–783.10.1515/BC.2004.101Search in Google Scholar
Meier, U.T. (1996). Comparison of the rat nucleolar protein nopp 140 with its yeast homolog SRP40. Differential phosphorylation in vertebrates and yeast. J. Biol. Chem.271, 19376–19384.Search in Google Scholar
Misteli, T. (1999). RNA splicing: what has phosphorylation got to do with it? Curr. Biol.9, R198–R200.10.1016/S0960-9822(99)80128-6Search in Google Scholar
Pind, M.T. and Watson, P.H. (2003). SR protein expression and CD44 splicing pattern in human breast tumours. Breast Cancer Res. Treat.79, 75–82.10.1023/A:1023338718974Search in Google Scholar
Roscigno, R.F. and Garcia-Blanco, M.A. (1995). SR proteins escort the U4/U6.U5tri-snRNP to the spliceosome. RNA1, 692–706.Search in Google Scholar
Scorilas, A., Black, M.H., Talieri, M., and Diamandis, E.P. (2000). Genomic organization, physical mapping and expression analysis of the human protein arginine methyltransferase 1 gene. Biochem. Biophys. Res. Commun.278, 349–359.10.1006/bbrc.2000.3807Search in Google Scholar PubMed
Scorilas, A., Kyriakopoulou, L., Katsaros, D. and Diamandis, E.P. (2001). Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer. Br. J. Cancer85, 190–198.10.1054/bjoc.2001.1885Search in Google Scholar PubMed PubMed Central
Screaton, G.R., Caceres, J.F., Mayeda, A., Bell, M.V., Plebanski, M, Jackson, D.G., Bell, J.I. and Krainer, A.R. (1995). Identification and characterization of three members of the human SR family of pre-mRNA splicing factors. EMBO J.14, 4336–4349.10.1002/j.1460-2075.1995.tb00108.xSearch in Google Scholar PubMed PubMed Central
Stickeler, E., Kittrell, F., Medina, D. and Berget, S.M. (1999). Stage-specific changes in SR splicing factors and alternative splicing in mammary tumorigenesis. Oncogene18, 3574–3582.10.1038/sj.onc.1202671Search in Google Scholar PubMed
Tacke, R., Chen, Y. and Manley, J.L. (1997). Sequence-specific RNA binding by an SR protein requires RS domain phosphorylation: creation of an SRp40–specific RNA binding by an RS protein requires RS domain phosphorylation: creation of an SRp40–specific splicing enhancer. Proc. Natl. Acad. Sci. USA94, 1148–1153.10.1073/pnas.94.4.1148Search in Google Scholar PubMed PubMed Central
Tanner, S., Stagljar, I., Georgiev, O., Schaffner, W. and Bourquin, J.P. (1997). A novel SR-related protein specifically interacts with the carboxy-terminal domain (CTD) of RNA polymerase II through a conserved interaction domain. Biol. Chem.378, 565–571.Search in Google Scholar
Xiao, S.H. and Manley, J.L. (1998). Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2. EMBO J.17, 6359–6367.10.1093/emboj/17.21.6359Search in Google Scholar PubMed PubMed Central
Yuryev, A., Patturajan, M., Litingtung, Y., Joshi, R.V., Gentile, C., Gebara, M. and Corden, J.L. (1996). The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins. Proc. Natl. Acad. Sci. USA93, 6975–6980.10.1073/pnas.93.14.6975Search in Google Scholar PubMed PubMed Central
Zahler, A.M., Neugebauer, K.M., Lane, W.S. and Roth, M.B. (1993). Distinct functions of SR proteins in alternative premRNA splicing. Science260, 219–222.10.1126/science.8385799Search in Google Scholar PubMed
Zhang, D. L., Sun, X.J., Ling, L.J., Chen, R. S. and Ma, D.L. (2002). Molecular cloning, characterization, chromosomal assignment, genomic organization and verification of SFRS12(SRrp508), a novel member of human SR protein superfamily and a human homolog of rat SRrp86. Yi Chuan Xue Bao29, 377–383.Search in Google Scholar
© Walter de Gruyter