SRSF3 (serine/arginine-rich splicing factor 3)

2012-05-01   Rong Jia , Zhi-Ming Zheng 

School of Stomatology Wuhan University, PR. China (RJ); Tumor Virus RNA Biology Section, HIV, AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA (ZMZ)




Atlas Image
Diagram of genomic structure of SRSF3 gene. The numbers above the diagram are the nucleotide positions in SRSF3 gene. The open boxes and broken lines represent exons and introns, respectively.


SRSF3 gene contains 6 exons and spans 10155 bp on the plus (+) strand of the short arm of chromosome 6.


SRSF3 mRNA is in size of 3144 nts and encodes a protein with 164 amino acid residues. By including an alternative exon between exon 3 and exon 4, SRSF3 pre-mRNA could generate additional isoform of SRSF3 transcript.




Atlas Image
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.


164 amino acid residues, 20 kDa.


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.


SRSF3 is a shuttling protein between nucleus and cytoplasm.


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).


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.



There is one mutation which causes amino acid residue change according to NCBI dbSNP database.

Implicated in

Entity name
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.


Pubmed IDLast YearTitleAuthors
171833662007A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation.Bedard KM et al
189460432008Genes involved in pre-mRNA 3'-end formation and transcription termination revealed by a lin-15 operon Muv suppressor screen.Cui M et al
126674642003SR splicing factors serve as adapter proteins for TAP-dependent mRNA export.Huang Y et al
113367122001Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA.Huang Y et al
211795882010SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance.Jia R et al
189457602009Control of the papillomavirus early-to-late switch by differentially expressed SRp20.Jia R et al
93056491997The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation.Jumaa H et al
97105811998Regulation of alternative polyadenylation by U1 snRNPs and SRp20.Lou H et al
220448812012Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons.Wang Z et al
170285902006RNA polymerase II C-terminal domain mediates regulation of alternative splicing by la Mata M et al

Other Information

Locus ID:

NCBI: 6428
MIM: 603364
HGNC: 10785
Ensembl: ENSG00000112081


dbSNP: 6428
ClinVar: 6428
TCGA: ENSG00000112081


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
Gene ExpressionREACTOMER-HSA-74160
RNA Polymerase II TranscriptionREACTOMER-HSA-73857
RNA Polymerase II Transcription TerminationREACTOMER-HSA-73856
Cleavage of Growing Transcript in the Termination RegionREACTOMER-HSA-109688
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163
mRNA 3'-end processingREACTOMER-HSA-72187
Transport of Mature Transcript to CytoplasmREACTOMER-HSA-72202
Transport of Mature mRNA derived from an Intron-Containing TranscriptREACTOMER-HSA-159236

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
268769372016Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.262
171833662007A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation.91
211795882010SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance.78
170285902006RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20.77
192509062009Chromatin binding of SRp20 and ASF/SF2 and dissociation from mitotic chromosomes is modulated by histone H3 serine 10 phosphorylation.74
190473692009SRp20 and CUG-BP1 modulate insulin receptor exon 11 alternative splicing.47
227773582013Downregulation of splicing factor SRSF3 induces p53β, an alternatively spliced isoform of p53 that promotes cellular senescence.44
189457602009Control of the papillomavirus early-to-late switch by differentially expressed SRp20.43
208562012011Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer.39
196024822009Antagonistic SR proteins regulate alternative splicing of tumor-related Rac1b downstream of the PI3-kinase and Wnt pathways.34


Rong Jia ; Zhi-Ming Zheng

SRSF3 (serine/arginine-rich splicing factor 3)

Atlas Genet Cytogenet Oncol Haematol. 2012-05-01

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