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Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Short Communication
SRSF3 (serine/arginine-rich splicing factor 3)
Rong Jia, Zhi-Ming Zheng
School of Stomatology Wuhan University, PR. China (RJ), Tumor Virus RNA Biology Section, HIV and
AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD
20892, USA (ZMZ)
Published in Atlas Database: May 2012
Online updated version : http://AtlasGeneticsOncology.org/Genes/SRSF3ID42279ch6p21.html
DOI: 10.4267/2042/48232
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Expression
Other names: SFRS3, SRp20
HGNC (Hugo): SRSF3
Location: 6p21.31
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.
DNA/RNA
Description
SRSF3 gene contains 6 exons and spans 10155 bp on
the plus (+) strand of the short arm of chromosome 6.
Transcription
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.
Localisation
SRSF3 is a shuttling protein between nucleus and
cytoplasm.
Pseudogene
Function
No.
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 differentiationdependent manner.
Protein
Description
164 amino acid residues, 20 kDa.
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.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
838
SRSF3 (serine/arginine-rich splicing factor 3)
Jia R, Zheng ZM
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.
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/Crich 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).
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.
Mutations
Note
There is one mutation which causes amino acid residue
change according to NCBI dbSNP database.
Implicated in
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.
References
Jumaa H, Nielsen PJ. The splicing factor SRp20 modifies
splicing of its own mRNA and ASF/SF2 antagonizes this
regulation. EMBO J. 1997 Aug 15;16(16):5077-85
Lou H, Neugebauer KM, Gagel RF, Berget SM. Regulation of
alternative polyadenylation by U1 snRNPs and SRp20. Mol
Cell Biol. 1998 Sep;18(9):4977-85
Huang Y, Steitz JA. Splicing factors SRp20 and 9G8 promote
the nucleocytoplasmic export of mRNA. Mol Cell. 2001
Apr;7(4):899-905
Homology
Huang Y, Gattoni R, Stévenin J, Steitz JA. SR splicing factors
serve as adapter proteins for TAP-dependent mRNA export.
Mol Cell. 2003 Mar;11(3):837-43
Human SRSF3 protein is highly conserved in
chimpanzee, dog, sheep, cow, mouse, rat, chicken,
zebrafish and so on. SRSF3 is the smallest member of
de la Mata M, Kornblihtt AR. RNA polymerase II C-terminal
domain mediates regulation of alternative splicing by SRp20.
Nat Struct Mol Biol. 2006 Nov;13(11):973-80
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
839
SRSF3 (serine/arginine-rich splicing factor 3)
Jia R, Zheng ZM
Bedard KM, Daijogo S, Semler BL. A nucleo-cytoplasmic SR
protein functions in viral IRES-mediated translation initiation.
EMBO J. 2007 Jan 24;26(2):459-67
Jia R, Li C, McCoy JP, Deng CX, Zheng ZM. SRp20 is a protooncogene critical for cell proliferation and tumor induction and
maintenance. Int J Biol Sci. 2010 Dec 15;6(7):806-26
Cui M, Allen MA, Larsen A, Macmorris M, Han M, Blumenthal
T. Genes involved in pre-mRNA 3'-end formation and
transcription termination revealed by a lin-15 operon Muv
suppressor screen. Proc Natl Acad Sci U S A. 2008 Oct
28;105(43):16665-70
Wang Z, Chatterjee D, Jeon HY, Akerman M, Vander Heiden
MG, Cantley LC, Krainer AR. Exon-centric regulation of
pyruvate kinase M alternative splicing via mutually exclusive
exons. J Mol Cell Biol. 2012 Apr;4(2):79-87
This article should be referenced as such:
Jia R, Liu X, Tao M, Kruhlak M, Guo M, Meyers C, Baker CC,
Zheng ZM. Control of the papillomavirus early-to-late switch by
differentially expressed SRp20. J Virol. 2009 Jan;83(1):167-80
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
Jia R, Zheng ZM. SRSF3 (serine/arginine-rich splicing factor
3). Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11):838840.
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