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| | Diagram of protein structure of SRSF3. The numbers below the diagram are the amino acid positions in SRSF3 protein. SRSF3 has an RNA recognition motifs (RRM) in the N-terminus and an arginine/serine-rich domain (RS) at the C-terminus. RRM motif identifies and binds specific RNA sequences. RS domain interacts with other proteins and facilitates recruitment of the spliceosomal components. The serine residues of the RS domain can be phosphorylated. |
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| Description | 164 amino acid residues, 20 kDa. |
| Expression | Expression of SRSF3 varies significantly in different cell types. For example, the expression of SRSF3 is abundant in the undifferentiated or intermediately differentiated keratinocytes in the basal and parabasal layers, but drops significantly in terminally differentiated keratinocytes in the superficial layers of the cervix or skin. In general, normal cells like muscle or nerve cells have no or little expression of SRSF3. In contrast, malignant tumor cells express remarkable amount of SRSF3 when compared to their normal counterparts. |
| Localisation | SRSF3 is a shuttling protein between nucleus and cytoplasm. |
| Function | SRSF3 is a splicing factor and involved in the regulation of RNA splicing. It affects alternative splicing by interacting with RNA cis-elements in a concentration and cell differentiation-dependent manner. Moreover, SRSF3 plays important roles in RNA export from nuclear to cytoplasm, termination of transcription, alternative RNA polyadenylation, and protein translation. SRSF3 is required for embryonic development and cell cycle progression. SRSF3 at increased expression is tumorigenic and is required for tumor initiation, progression, and maintenance. Alternative splicing of pre-mRNA SRSF3 controls viral early to late switch by regulation of gene expression of bovine papillomavirus type 1 and human papillomavirus through interaction with A/C-rich RNA elements (Jia et al., 2009). SRSF3 promotes the inclusion of exon 4 of its own mRNA and reduces the expression of full length SRSF3 protein (Juma and Nielsen, 1997). SRSF3 activates the inclusion of exon 10 of PK-M gene to promote the expression of oncogenic M2 isoform (Wang et al., 2012). SRSF3 inhibits the inclusion of a fibronectin cassette exon in the mature mRNA by interacting with RNA polymerase II C-terminal domain (de la Mata and Kornblihtt, 2006). Termination of transcription SRSF3 plays a role in termination of transcription by binding to RNA downstream of the cleavage site, facilitating its degradation, and the release of Pol II from template DNA (Cui et al., 2008). Alternative polyadenylation The 3'-terminal exon 4 of calcitonin pre-mRNA contains an alternative polyadenylation site. SRSF3 affects the inclusion of exon 4 and alternative polyadenylation by the interaction with CstF (Lou et al., 1998). RNA export SRSF3 associates with TAP promoting the export of intronless mRNA of histone H2a gene by interacting with a 22-nt RNA element (Huang et al., 2003; Huang and Steitz, 2001). Protein translation SRSF3 is required for poliovirus translation initiation. SRSF3 binds to internal ribosome entry site (IRES) of a viral RNA by interaction with PCBP2 (Bedard et al., 2007). |
| Homology | Human SRSF3 protein is highly conserved in chimpanzee, dog, sheep, cow, mouse, rat, chicken, zebrafish and so on. SRSF3 is the smallest member of SR (serine/arginine-rich) family and shares a high homology with other members. All of SR proteins contain at least one RRM and one downstream RS domain enriched in repeating arginine-serine dipeptides. |
| Note | |
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| Entity | Cancer |
| Note | SRSF3 is a protooncogene. Overexpression of SRSF3 has been found in various cancers, including cervix, lung, breast, stomach, skin, bladder, colon, liver, thyroid, and kidney; and in various soft tissue tumors, including B-cell lymphoma, rhabdomyosarcoma, hemangioendothelioma, hemangiopericytoma, neurofibroma, neurilemmoma, liposarcoma, leiomyosarcoma, histiocytoma, and synovial sarcoma. SRSF3 at overexpression has transformation activity for MEF/3T3 cells, a mouse embroynic fibroblast cell line. SRSF3 controls cell cycle progression and thereby cell proliferation presumably by regulating the expression of forkhead box transcription factor M1 (FoxM1), PLK1 and Cdc25B. |
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| A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation. |
| Bedard KM, Daijogo S, Semler BL. |
| EMBO J. 2007 Jan 24;26(2):459-67. Epub 2006 Dec 21. |
| PMID 17183366 |
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| Genes involved in pre-mRNA 3'-end formation and transcription termination revealed by a lin-15 operon Muv suppressor screen. |
| Cui M, Allen MA, Larsen A, Macmorris M, Han M, Blumenthal T. |
| Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16665-70. Epub 2008 Oct 22. |
| PMID 18946043 |
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| SR splicing factors serve as adapter proteins for TAP-dependent mRNA export. |
| Huang Y, Gattoni R, Stevenin J, Steitz JA. |
| Mol Cell. 2003 Mar;11(3):837-43. |
| PMID 12667464 |
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| Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. |
| Huang Y, Steitz JA. |
| Mol Cell. 2001 Apr;7(4):899-905. |
| PMID 11336712 |
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| SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance. |
| Jia R, Li C, McCoy JP, Deng CX, Zheng ZM. |
| Int J Biol Sci. 2010 Dec 15;6(7):806-26. |
| PMID 21179588 |
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| Control of the papillomavirus early-to-late switch by differentially expressed SRp20. |
| Jia R, Liu X, Tao M, Kruhlak M, Guo M, Meyers C, Baker CC, Zheng ZM. |
| J Virol. 2009 Jan;83(1):167-80. Epub 2008 Oct 22. |
| PMID 18945760 |
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| The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation. |
| Jumaa H, Nielsen PJ. |
| EMBO J. 1997 Aug 15;16(16):5077-85. |
| PMID 9305649 |
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| Regulation of alternative polyadenylation by U1 snRNPs and SRp20. |
| Lou H, Neugebauer KM, Gagel RF, Berget SM. |
| Mol Cell Biol. 1998 Sep;18(9):4977-85. |
| PMID 9710581 |
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| Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons. |
| Wang Z, Chatterjee D, Jeon HY, Akerman M, Vander Heiden MG, Cantley LC, Krainer AR. |
| J Mol Cell Biol. 2012 Apr;4(2):79-87. Epub 2011 Nov 1. |
| PMID 22044881 |
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| RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20. |
| de la Mata M, Kornblihtt AR. |
| Nat Struct Mol Biol. 2006 Nov;13(11):973-80. Epub 2006 Oct 8. |
| PMID 17028590 |
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