SR Proteins


Members of the serine/arginine‐rich (SR) protein family have several important functions in mRNA biogenesis. SR proteins are essential splicing factors that also participate in the regulation of alternative splicing and the export of mRNAs from the nucleus to the cytoplasm.

Keywords: SR protein; splicing; alternative splicing; RNA‐binding protein; mRNA export

Figure 1.

Organization of the human genes that encode SR proteins. The exon–intron organization of each human SR protein gene is shown. Noncoding portions of each exon are represented by white boxes, coding portions of exons are indicated by black boxes. Alternatively spliced exons are indicated in gray. The splicing of the alternative exons is autoregulated by the SR protein encoded by the gene. The exons and introns for each gene are drawn to scale and the size of each gene is indicated.

Figure 2.

The human SR protein family. The structural organization of the nine human SR proteins is shown. RRM: RNA recognition motif; RRMH: RRM homology; Zn: zinc‐knuckle; RS: arginine/serine‐rich domain.

Figure 3.

Exon‐dependent functions of SR proteins. (a) ESE‐bound SR proteins may function by activating upstream 3′ splice sites. This can be achieved through recruitment of the general splicing factor U2AF, through interactions with the splicing coactivator SRm160, or by antagonizing the activity of splicing inhibitors. (b) Alternative 5′ splice sites may be activated on the recruitment of U1 snRNP by ESE‐bound SR proteins. (c) SR proteins may function in constitutive splicing by simultaneously interacting with U2AF bound to the upstream 3′ splice site and U1 snRNP bound to the downstream 5′ splice site. Py: pyrimidine tract.

Figure 4.

Exon‐independent functions of SR proteins. SR proteins have two exon‐independent functions. First, SR proteins facilitate splice‐site pairing by simultaneously interacting with U1 snRNP and U2AF across the intron. Second, SR proteins in the partially assembled spliceosome are involved in recruiting the U4/U6•U5 tri‐snRNP.

Figure 5.

Models of mRNA export. (a) Intronless mRNAs such as H2a contain high‐affinity binding sites (black box) for SR proteins that shuttle continuously between the nucleus and the cytoplasm. Association of shuttling SR proteins with the intronless mRNA leads to nuclear export via an unknown pathway. (b) Before splicing, nascent pre‐mRNAs are coated by hnRNPs (heterogeneous nuclear ribonucleoproteins). During spliceosomal assembly, SR proteins bind to each exon with sufficient affinity to replace hnRNPs effectively. During intron removal, conserved export factors, in particular ALY/REF, are recruited to the exons. Because of their association with exonic sequences throughout the splicing cycle, SR proteins may assist in linking pre‐mRNA splicing to mRNA export either directly by interacting with the export machinery or indirectly by inhibiting the association of nuclear retention factors such as hnRNPs with the mRNA. The spliced mRNA is then exported from the nucleus via a pathway involving TAP/p15, Gle, Gle2 or Dbp5 (nuclear export factors).



Huang Y and Steitz JA (2001) Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Molecular Cell 7: 899–905.

Kanopka A, Muhlemann O and Akusjarvi G (1996) Inhibition by SR proteins of splicing of a regulated adenovirus pre‐mRNA. Nature 381: 535–538.

Kohtz JD, Jamison SF, Will CL, et al. (1994) Protein–protein interactions and 5′ splice site recognition in mammalian mRNA precursors. Nature 368: 119–124.

Liu HX, Zhang M and Krainer AR (1998) Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes and Development 12: 1998–2012.

Mayeda A, Screaton GR, Chandler SD, Fu XD and Krainer AR (1999) Substrate specificities of SR proteins in constitutive splicing are determined by their RNA recognition motifs and composite pre‐mRNA exonic elements. Molecular and Cellular Biology 19: 1853–1863.

Ryner LC, Goodwin SF, Castrillon DH, et al. (1996) Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell 87: 1079–1089.

Sanford JR and Bruzik JP (1999) Developmental regulation of SR protein phosphorylation and activity. Genes and Development 13: 1513–1518.

Wu JY and Maniatis T (1993) Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell 75: 1061–1070.

Zahler AM, Lane WS, Stolk JA and Roth MB (1992) SR proteins: a conserved family of pre‐mRNA splicing factors. Genes and Development 6: 837–847.

Zuo P and Maniatis T (1996) The splicing factor U2AF35 mediates critical protein–protein interactions in constitutive and enhancer‐dependent splicing. Genes and Development 10: 1356–1368.

Further Reading

Blencowe BJ, Bowman JAL, McCracken S and Ronina E (1999) SR‐related proteins and the processing of messenger RNA precursors. Biochemistry and Cell Biology 77: 277–291.

Caceres JF, Screaton GR and Krainer AR (1998) A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes and Development 12: 55–66.

Graveley BR (2000) Sorting out the complexity of SR protein functions. RNA 6: 1197–1211.

Kan JLC and Green MR (1999) Pre‐mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor. Genes and Development 13: 462–471.

Li Y and Blencowe BJ (1999) Distinct factor requirements for exonic splicing enhancer function and binding of U2AF to the polypyrimidine tract. Journal of Biological Chemistry 274: 35074–35079.

Prasad J, Colwill K, Pawson T and Manley JL (1999) The protein kinase Clk/Sty directly modulates SR protein activity: both hyper‐ and hypophosphorylation inhibit splicing. Molecular and Cellular Biology 19: 6991–7000.

Reed R and Magni K (2001) A new view of mRNA export: separating the wheat from the chaff. Nature Cell Biology 3: E201–E204.

Roscigno RF and Garcia‐Blanco MA (1995) SR proteins escort the U4/U6•U5 tri‐snRNP to the spliceosome. RNA 1: 692–706.

Schaal TD and Maniatis T (1999) Multiple distinct splicing enhancers in the protein‐coding sequences of a constitutively spliced pre‐mRNA. Molecular and Cellular Biology 19: 261–273.

Spector DL (1993) Macromolecular domains within the cell nucleus. Annual Reviews in Cell Biology 9: 265–315.

Web Links

Splicing factor, arginine/serine‐rich 1 (SFRS1); LocusID: 6426. Locus Link:

Splicing factor, arginine/serine‐rich 1 (SFRS1); MIM number: 600812. OMIM:‐post/Omim/dispmim?600812

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How to Cite close
Graveley, Brenton R, and Hertel, Klemens J(Sep 2005) SR Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005039]