* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Gene Section SRSF1 (serine/arginine rich splicing factor 1) -
RNA silencing wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Transcription factor wikipedia , lookup
Protein moonlighting wikipedia , lookup
Gene expression profiling wikipedia , lookup
Oncogenomics wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
History of RNA biology wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Non-coding RNA wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Long non-coding RNA wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Epitranscriptome wikipedia , lookup
Mir-92 microRNA precursor family wikipedia , lookup
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Short Communication SRSF1 (serine/arginine-rich splicing factor 1) Ruben Pio Department of Biochemistry and Division of Oncology (CIMA), University of Navarra, Pamplona, Spain (RP) Published in Atlas Database: November 2011 Online updated version : http://AtlasGeneticsOncology.org/Genes/SRSF1ID47631ch17q22.html DOI: 10.4267/2042/47303 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 Other names: ASF, FLJ53078, MGC5228, SF2, SF2p33, SFRS1, SRp30a HGNC (Hugo): SRSF1 Location: 17q22 Schematic diagram of SF2/ASF protein. SF2/ASF has a modular structure with two RNA recognition motifs (RRM) that provide RNA-binding specificity and one arginine/serine-rich domain (RS), involved in protein-protein interactions that facilitate recruitment of the spliceosome. The RS domain acts also as a nuclear localization signal, controlling the subcellular localization of SF2/ASF. The protein can be phosphorilated in Ser residues in the C-terminal RS domain. DNA/RNA Expression SF2/ASF is constitutively expressed in all cell types. However, there are differences in expression levels between cell types and organs. Moreover, in some pathological conditions the expression levels are altered. Genomic structure of the SRSF1 gene. The black area indicates the coding sequence. Description The SRSF1 locus spans 6424 bp on the minus (-) strand of the long arm of chromosome 17 and is composed of 4 exons. Localisation SF2/ASF is a shuttling protein with a high mobility between the nucleus and the cytoplasm. In the nucleus, SF2/ASF is concentrated in speckles and when transcription is activated it accumulates at the sites of transcription. Transcription ASF-1 (SF2) contains 4 exons (248 aa). Two additional cDNAs generated by alternative 3' splice-site use or by intron retention have been described and are designated ASF-2 (292 aa) and ASF-3 (201 aa), respectively. However, ASF/SF2 is the only isoform expressed at detectable levels. Function SF2/ASF modulates both constitutive and alternative pre-mRNA splicing. The function of SF2/ASF in splicing depends on the pre-mRNA sequence and the cellular context. Cis-acting sequences and trans-acting factors modulate SF2/ASF activity. For example, SF2/ASF antagonizes the activity of hnRNP A/B proteins in splice site selection. An excess of hnRNP A1 favors distal 5' splice sites, whereas SF2/ASF promotes the use of proximal 5' splice sites. Pseudogene No known pseudogenes. Protein Description 248 amino acids, 28 kDa. Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4) 286 SRSF1 (serine/arginine-rich splicing factor 1) Pio R SF2/ASF is also involved in transcription, mRNA export, nonsense-mediated mRNA decay, and translation. Cardiac remodeling Note SF2/ASF has a role in cardiac remodeling. ASF/SF2 is a key regulator of alternative splicing events during postnatal heart remodeling. Homology SF2/ASF shares a high homology with other members of the SR family. SR proteins are conserved across vertebrates and invertebrates. They contain one or two copies of an RNA recognition motif (RRM) at the amino-terminus, spaced by a series of glycine residues that may form a flexible hinge, and a carboxy-terminal highly charged SR domain. Retroviral splicing Note SF2/ASF regulates retroviral splicing. SF2/ASF has been implicated in the regulation of retroviral splicing in Rous sarcoma virus, HIV-1 and HPV-16. Mutations Cell motility Note No mutations have been reported. Gene amplification has been found in some tumor types. Note SF2/ASF activates epithelial to mesenchymal transition. DeltaRon, a splicing isoform of the tyrosine kinase receptor Ron, increases motility. DeltaRon is generated by the skipping of exon 11. SF2/ASF, by controlling the production of DeltaRon, activates epithelial to mesenchymal transition, leading to cell locomotion. Implicated in Various cancers Note SF2/ASF acts as an oncogene. SF2/ASF is upregulated in various human tumors, including lung, colon, kidney, liver, pancreas, ovary, cervix, and breast. Upregulation is sometimes associated with gene amplification. Overexpression of SF2/ASF is sufficient to transform immortal rodent fibroblasts. mTORC1 activation may be essential for SF2/ASF-mediated transformation. SF2/ASF-bound mRNAs recruit the mTOR kinase, resulting in the phosphorylation and release of 4E-BP, leading to translation initiation. Clinical tumors with SF2/ASF up-regulation may be especially sensitive to mTOR inhibitors. References Ge H, Manley JL. A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro. Cell. 1990 Jul 13;62(1):25-34 Krainer AR, Conway GC, Kozak D. Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes Dev. 1990a Jul;4(7):1158-71 Krainer AR, Conway GC, Kozak D. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites. Cell. 1990b Jul 13;62(1):35-42 Ge H, Zuo P, Manley JL. Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators. Cell. 1991 Jul 26;66(2):373-82 Non-small cell lung cancer (NSCLC) Note SF2/ASF and survivin expression are involved in nonsmall cell lung cancer progression. SF2/ASF is overexpressed in lung cancer cell lines and human NSCLC specimens. SF2/ASF controls the expression of survivin through the activation of the mTOR pathway. Mayeda A, Krainer AR. Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2. Cell. 1992 Jan 24;68(2):365-75 Zahler AM, Lane WS, Stolk JA, Roth MB. SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev. 1992 May;6(5):837-47 Zuo P, Manley JL. The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5' splice sites. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3363-7 Prostate cancer Misteli T, Cáceres JF, Spector DL. The dynamics of a premRNA splicing factor in living cells. Nature. 1997 May 29;387(6632):523-7 Note Cyclin D1b oncogene is induced by SF2/ASF. SF2/ASF associates with cyclin D1b mRNA, an alternative splicing of the CCND1 transcript with enhanced oncogenic functions. SF2/ASF expression correlates with cyclin D1b in human prostate cancer. Cáceres JF, Screaton GR, Krainer AR. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes Dev. 1998 Jan 1;12(1):55-66 Hanamura A, Cáceres JF, Mayeda A, Franza BR Jr, Krainer AR. Regulated tissue-specific expression of antagonistic premRNA splicing factors. RNA. 1998 Apr;4(4):430-44 Cystic fibrosis Note Aberrant regulation of CFTR exon 9 alternative splicing by splicing factors may be associated with cystic fibrosis. SF2/ASF binds to an intronic splicing silencer of exon 9 of CFTR and promotes exon exclusion. Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4) McNally LM, McNally MT. An RNA splicing enhancer-like sequence is a component of a splicing inhibitor element from Rous sarcoma virus. Mol Cell Biol. 1998 Jun;18(6):3103-11 Kruhlak MJ, Lever MA, Fischle W, Verdin E, Bazett-Jones DP, Hendzel MJ. Reduced mobility of the alternate splicing factor 287 SRSF1 (serine/arginine-rich splicing factor 1) Pio R (ASF) through the nucleoplasm and steady state speckle compartments. J Cell Biol. 2000 Jul 10;150(1):41-51 Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR. The gene encoding the splicing factor SF2/ASF is a protooncogene. Nat Struct Mol Biol. 2007 Mar;14(3):185-93 Pagani F, Buratti E, Stuani C, Romano M, Zuccato E, Niksic M, Giglio L, Faraguna D, Baralle FE. Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element. J Biol Chem. 2000 Jul 14;275(28):21041-7 Karni R, Hippo Y, Lowe SW, Krainer AR. The splicing-factor oncoprotein SF2/ASF activates mTORC1. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15323-7 Fay J, Kelehan P, Lambkin H, Schwartz S. Increased expression of cellular RNA-binding proteins in HPV-induced neoplasia and cervical cancer. J Med Virol. 2009 May;81(5):897-907 Aubol BE, Chakrabarti S, Ngo J, Shaffer J, Nolen B, Fu XD, Ghosh G, Adams JA. Processive phosphorylation of alternative splicing factor/splicing factor 2. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12601-6 Long JC, Caceres JF. The SR protein family of splicing factors: master regulators of gene expression. Biochem J. 2009 Jan 1;417(1):15-27 Fischer DC, Noack K, Runnebaum IB, Watermann DO, Kieback DG, Stamm S, Stickeler E. Expression of splicing factors in human ovarian cancer. Oncol Rep. 2004 May;11(5):1085-90 Ezponda T, Pajares MJ, Agorreta J, Echeveste JI, LópezPicazo JM, Torre W, Pio R, Montuenga LM. The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression. Clin Cancer Res. 2010 Aug 15;16(16):4113-25 Ghigna C, Giordano S, Shen H, Benvenuto F, Castiglioni F, Comoglio PM, Green MR, Riva S, Biamonti G. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol Cell. 2005 Dec 22;20(6):881-90 Olshavsky NA, Comstock CE, Schiewer MJ, Augello MA, Hyslop T, Sette C, Zhang J, Parysek LM, Knudsen KE. Identification of ASF/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene. Cancer Res. 2010 May 15;70(10):3975-84 Jacquenet S, Decimo D, Muriaux D, Darlix JL. Dual effect of the SR proteins ASF/SF2, SC35 and 9G8 on HIV-1 RNA splicing and virion production. Retrovirology. 2005 May 22;2:33 Xu X, Yang D, Ding JH, Wang W, Chu PH, Dalton ND, Wang HY, Bermingham JR Jr, Ye Z, Liu F, Rosenfeld MG, Manley JL, Ross J Jr, Chen J, Xiao RP, Cheng H, Fu XD. ASF/SF2regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Cell. 2005 Jan 14;120(1):59-72 Somberg M, Schwartz S. Multiple ASF/SF2 sites in the human papillomavirus type 16 (HPV-16) E4-coding region promote splicing to the most commonly used 3'-splice site on the HPV16 genome. J Virol. 2010 Aug;84(16):8219-30 This article should be referenced as such: Buratti E, Stuani C, De Prato G, Baralle FE. SR proteinmediated inhibition of CFTR exon 9 inclusion: molecular characterization of the intronic splicing silencer. Nucleic Acids Res. 2007;35(13):4359-68 Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4) Pio R. SRSF1 (serine/arginine-rich splicing factor 1). Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4):286-288. 288