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Gene Review

SRSF2  -  serine/arginine-rich splicing factor 2

Homo sapiens

Synonyms: PR264, Protein PR264, SC-35, SC35, SFRS2, ...
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Disease relevance of SFRS2


High impact information on SFRS2

  • These SR proteins, which include SC35 and SF2/ASF, are conserved from Drosophila to man, are required for early steps of spliceosome assembly and can influence splice-site selections [6].
  • I report here that SC35 was sufficient on its own to form a committed complex with human beta-globin pre-mRNA [6].
  • Spliceosome assembly factor SC-35 localized within the center of individual domains [7].
  • A search of the DNA sequence database revealed that the thymus-specific exon (ET) of the c-myb proto-oncogene is encoded on the antisense strand of the SC35 gene [8].
  • We present evidence, based on both in vivo and in vitro experiments, that the skipping of this exon is due to the disruption of an SC35-dependent splicing enhancer within exon 51 [9].

Biological context of SFRS2


Anatomical context of SFRS2

  • The results showed a decrease of snRNPs and SC-35 in the karyoplasm as the oocytes progress from a transcriptionally active to the inactive state [15].
  • Here, we show that overexpression of SC35 in HeLa cells results in a significant decrease of endogenous SC35 mRNA levels along with changes in the relative abundance of SC35 alternatively spliced mRNAs [13].
  • Consistently, ectopic overexpression of this splicing factor enhanced the use of the cryptic splice site, whereas small interfering RNA-mediated reduction of the SC35 protein levels in primary fibroblasts from the patient resulted in the almost complete disappearance of the aberrantly spliced E1alpha PDH mRNA [1].
  • On account of the SC35-immunostaining patterns no distinction of subpopulations of astrocytes is possible [16].
  • Transient transfection of the U1 snRNP 70K protein into COS cells induced nuclear reorganization and redistribution of the splicing factor SC-35, whereas hnRNP proteins were not affected [17].

Associations of SFRS2 with chemical compounds

  • CIR was found to be colocalized with SC35 and PAP-1 in nuclear speckles [18].
  • Actinomycin D treatment caused the relocalisation of alpha B-crystallin along with Sm and SC35 to a smaller number of more distinct spots, suggesting a link between speckle localisation and the transcriptional status of the cells [19].
  • The human pre-mRNA splicing factors SF2 and SC35 have similar electrophoretic mobilities, and both of them contain an N-terminal ribonucleoprotein (RNP)-type RNA-recognition motif and a C-terminal arginine/serine-rich domain [20].
  • While a subset of serine/arginine protein splicing factors, including SF2/ASF, SC35, and SRp20, is efficiently recruited to the tau gene when exon 10 is included, these factors are less frequently associated with tau transcription sites when exon 10 is excluded [21].
  • Affinity-purified antibodies eluted from recombinant proteins recognized a 64-kD nuclear protein in Western blotting and decorated the nucleoplasm in a speckled-network fashion in immunofluorescence, colocalizing with antibodies to pre-mRNA splicing factor SC35 and uridine-rich small nuclear RNAs [22].

Co-localisations of SFRS2


Other interactions of SFRS2

  • We conclude that exon 6A recognition in vitro depends on the ratio of the ASF/SF2 to SC35 SR proteins [24].
  • This similarity was confirmed by the fact that purified human SC35 also rescues the 9G8-depleted extract [25].
  • The distribution of two splicing components (snRNP and SC-35) and coilin were studied by immunogold/electron microscopy in human oocytes from antral follicles at different levels of transcriptional activity (i.e., active, intermediate, and inactive) [15].
  • In addition, transiently expressed intron-containing beta-globin RNAs were shown to distribute to weak anti-SC-35 staining in a manner similar to that of HIV-1 RNAs [3].
  • The molecular cloning of a 4.1 cDNA encoding the isoform designated 4.1E has allowed us to show that this protein is targeted to the nucleus, that it associates with the splicing factor U2AF35, and that its overexpression induces the redistribution of the splicing factor SC35 [26].

Analytical, diagnostic and therapeutic context of SFRS2


  1. The SR protein SC35 is responsible for aberrant splicing of the E1alpha pyruvate dehydrogenase mRNA in a case of mental retardation with lactic acidosis. Gabut, M., Miné, M., Marsac, C., Brivet, M., Tazi, J., Soret, J. Mol. Cell. Biol. (2005) [Pubmed]
  2. Identification of a domain in human immunodeficiency virus type 1 rev that is required for functional activity and modulates association with subnuclear compartments containing splicing factor SC35. D'Agostino, D.M., Ferro, T., Zotti, L., Meggio, F., Pinna, L.A., Chieco-Bianchi, L., Ciminale, V. J. Virol. (2000) [Pubmed]
  3. Subcellular localization of human immunodeficiency virus type 1 RNAs, Rev, and the splicing factor SC-35. Bøe, S.O., Bjørndal, B., Røsok, B., Szilvay, A.M., Kalland, K.H. Virology (1998) [Pubmed]
  4. Mutation analysis of a putative sialyltransferase gene, the SFRS2 splicing factor gene and the c-myb ET-locus in two families with hereditary neuralgic amyotrophy (HNA). Kuhlenbaeumer, G., Meuleman, J., Schirmacher, A., Stoegbauer, F., Ringelstein, E.B., Wehnert, M., Hoeltzenbein, M., Broeckhoven, C.V., Timmerman, V. Ann. Hum. Genet. (1998) [Pubmed]
  5. Induced HMGA1a expression causes aberrant splicing of Presenilin-2 pre-mRNA in sporadic Alzheimer's disease. Manabe, T., Katayama, T., Sato, N., Gomi, F., Hitomi, J., Yanagita, T., Kudo, T., Honda, A., Mori, Y., Matsuzaki, S., Imaizumi, K., Mayeda, A., Tohyama, M. Cell Death Differ. (2003) [Pubmed]
  6. Specific commitment of different pre-mRNAs to splicing by single SR proteins. Fu, X.D. Nature (1993) [Pubmed]
  7. A three-dimensional view of precursor messenger RNA metabolism within the mammalian nucleus. Carter, K.C., Bowman, D., Carrington, W., Fogarty, K., McNeil, J.A., Fay, F.S., Lawrence, J.B. Science (1993) [Pubmed]
  8. Isolation of a complementary DNA that encodes the mammalian splicing factor SC35. Fu, X.D., Maniatis, T. Science (1992) [Pubmed]
  9. A nonsense mutation in the fibrillin-1 gene of a Marfan syndrome patient induces NMD and disrupts an exonic splicing enhancer. Caputi, M., Kendzior, R.J., Beemon, K.L. Genes Dev. (2002) [Pubmed]
  10. Alternative splicing of the adenylyl cyclase stimulatory G-protein G alpha(s) is regulated by SF2/ASF and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and involves the use of an unusual TG 3'-splice Site. Pollard, A.J., Krainer, A.R., Robson, S.C., Europe-Finner, G.N. J. Biol. Chem. (2002) [Pubmed]
  11. hnRNP A1 and the SR proteins ASF/SF2 and SC35 have antagonistic functions in splicing of beta-tropomyosin exon 6B. Expert-Bezançon, A., Sureau, A., Durosay, P., Salesse, R., Groeneveld, H., Lecaer, J.P., Marie, J. J. Biol. Chem. (2004) [Pubmed]
  12. The gene encoding human splicing factor 9G8. Structure, chromosomal localization, and expression of alternatively processed transcripts. Popielarz, M., Cavaloc, Y., Mattei, M.G., Gattoni, R., Stévenin, J. J. Biol. Chem. (1995) [Pubmed]
  13. SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs. Sureau, A., Gattoni, R., Dooghe, Y., Stévenin, J., Soret, J. EMBO J. (2001) [Pubmed]
  14. Regulation of Ich-1 pre-mRNA alternative splicing and apoptosis by mammalian splicing factors. Jiang, Z.H., Zhang, W.J., Rao, Y., Wu, J.Y. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  15. Dynamics of distribution of splicing components relative to the transcriptional state of human oocytes from antral follicles. Parfenov, V.N., Davis, D.S., Pochukalina, G.N., Kostyuchek, D., Murti, K.G. J. Cell. Biochem. (1998) [Pubmed]
  16. Immunolabelling of spliceosomes in sections and cultured astrocytes of human fetal brain tissue. Ulfig, N., Briese, V. Brain Dev. (1999) [Pubmed]
  17. Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA. Romac, J.M., Keene, J.D. Genes Dev. (1995) [Pubmed]
  18. CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing. Maita, H., Kitaura, H., Ariga, H., Iguchi-Ariga, S.M. Exp. Cell Res. (2005) [Pubmed]
  19. Nuclear speckle localisation of the small heat shock protein alpha B-crystallin and its inhibition by the R120G cardiomyopathy-linked mutation. van den IJssel, P., Wheelock, R., Prescott, A., Russell, P., Quinlan, R.A. Exp. Cell Res. (2003) [Pubmed]
  20. General splicing factors SF2 and SC35 have equivalent activities in vitro, and both affect alternative 5' and 3' splice site selection. Fu, X.D., Mayeda, A., Maniatis, T., Krainer, A.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  21. Differential recruitment of pre-mRNA splicing factors to alternatively spliced transcripts in vivo. Mabon, S.A., Misteli, T. PLoS Biol. (2005) [Pubmed]
  22. Novel nuclear autoantigen with splicing factor motifs identified with antibody from hepatocellular carcinoma. Imai, H., Chan, E.K., Kiyosawa, K., Fu, X.D., Tan, E.M. J. Clin. Invest. (1993) [Pubmed]
  23. Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factors. de Graaf, K., Hekerman, P., Spelten, O., Herrmann, A., Packman, L.C., Büssow, K., Müller-Newen, G., Becker, W. J. Biol. Chem. (2004) [Pubmed]
  24. The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the beta-tropomyosin alternative exon 6A. Gallego, M.E., Gattoni, R., Stévenin, J., Marie, J., Expert-Bezançon, A. EMBO J. (1997) [Pubmed]
  25. Characterization and cloning of the human splicing factor 9G8: a novel 35 kDa factor of the serine/arginine protein family. Cavaloc, Y., Popielarz, M., Fuchs, J.P., Gattoni, R., Stévenin, J. EMBO J. (1994) [Pubmed]
  26. Functional association of nuclear protein 4.1 with pre-mRNA splicing factors. Lallena, M.J., Martínez, C., Valcárcel, J., Correas, I. J. Cell. Sci. (1998) [Pubmed]
  27. Mimicking phosphorylation of the small heat-shock protein alphaB-crystallin recruits the F-box protein FBX4 to nuclear SC35 speckles. den Engelsman, J., Bennink, E.J., Doerwald, L., Onnekink, C., Wunderink, L., Andley, U.P., Kato, K., de Jong, W.W., Boelens, W.C. Eur. J. Biochem. (2004) [Pubmed]
  28. Expression of splicing factors in human ovarian cancer. Fischer, D.C., Noack, K., Runnebaum, I.B., Watermann, D.O., Kieback, D.G., Stamm, S., Stickeler, E. Oncol. Rep. (2004) [Pubmed]
  29. An exonic splicing enhancer offsets the atypical GU-rich 3' splice site of human apolipoprotein A-II exon 3. Arrisi-Mercado, P., Romano, M., Muro, A.F., Baralle, F.E. J. Biol. Chem. (2004) [Pubmed]
  30. Mta has properties of an RNA export protein and increases cytoplasmic accumulation of Epstein-Barr virus replication gene mRNA. Semmes, O.J., Chen, L., Sarisky, R.T., Gao, Z., Zhong, L., Hayward, S.D. J. Virol. (1998) [Pubmed]
  31. Detection of apoptosis in kidney biopsies of patients with D+ hemolytic uremic syndrome. Te Loo, D.M., Monnens, L.A., van den Heuvel, L.P., Gubler, M.C., Kockx, M.M. Pediatr. Res. (2001) [Pubmed]
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