| Gene Name | SRSF2 |
| HF Protein Name | Serine/arginine-rich splicing factor 2 |
| HF Function | SRSF2 is a key regulator of HPV16 oncoprotein expression |
| Uniprot ID | Q01130 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 6427 |
| Host Factor (HF) Name in Paper | SRSF2 |
| Gene synonyms | SFRS2 |
| Ensemble Gene ID | ENSG00000119383 |
| Ensemble Transcript | ENST00000359995 [Q01130-1];ENST00000392485 [Q01130-1];ENST00000452355 [Q01130-1];ENST00000508921 [Q01130-2];ENST00000585202 [Q01130-1] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000278, GO:0000381, GO:0000398, GO:0003714, GO:0003723, GO:0005080, GO:0005634, GO:0005654, GO:0005681, GO:0005829, GO:0006369, GO:0006397, GO:0006405, GO:0006406, GO:0008380, GO:0016607, GO:0031124, GO:0033197, GO:0035061, GO:0036002, GO:0070062, |
| MINT ID | Q01130 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 600813 |
| PANTHER ID | PTHR23147:SF16 |
| PDB ID(s) | 2KN4, 2LEA, 2LEB, 2LEC, |
| pfam ID | PF00076, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Human papillomavirus type 16 |
| Virus Short Name | HPV16 |
| Order | Unassigned |
| Virus Family | Papillomaviridae |
| Virus Subfamily | N.A. |
| Genus | Alphapapillomavirus |
| Species | Human papillomavirus 16 |
| Host | Human, monkeys |
| Cell Tropism | Epithelial cells of skin, mucous membranes |
| Associated Disease | Malignant tumours |
| Mode of Transmission | Sexual, indirect and direct contact, auto-inoculation |
| VIPR DB link | N.A. |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/121/papillomaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Papillomaviridae |
| Paper Title | Human Papillomavirus 16 Oncoprotein Expression Is Controlled by the Cellular Splicing Factor SRSF2 (SC35) |
| Author's Name | Melanie McFarlane, Alasdair I. MacDonald, Andrew Stevenson, Sheila V. Graham |
| Journal Name | Journal Of Virology |
| Pubmed ID | 25717103 |
| Abstract | High-risk human papillomaviruses (HR-HPV) cause anogenital cancers, including cervical cancer, and head and neck cancers. Human papillomavirus 16 (HPV16) is the most prevalent HR-HPV. HPV oncogenesis is driven by two viral oncoproteins, E6 and E7, which are expressed through alternative splicing of a polycistronic RNA to yield four major splice isoforms (E6 full length, E6*I, E6*II, E6*X). The production of multiple mRNA isoforms from a single gene is controlled by serine/arginine-rich splicing factors (SRSFs), and HPV16 infection induces overexpression of a subset of these, SRSFs 1, 2, and 3. In this study, we examined whether these proteins could control HPV16 oncoprotein expression. Small interfering RNA (siRNA) depletion experiments revealed that SRSF1 did not affect oncoprotein RNA levels. While SRSF3 knockdown caused some reduction in E6E7 expression, depletion of SRSF2 resulted in a significant loss of E6E7 RNAs, resulting in reduced levels of the E6-regulated p53 proteins and E7 oncoprotein itself. SRSF2 contributed to the tumor phenotype of HPV16-positive cervical cancer cells, as its depletion resulted in decreased cell proliferation, reduced colony formation, and increased apoptosis. SRSF2 did not affect transcription from the P97 promoter that controls viral oncoprotein expression. Rather, RNA decay experiments showed that SRSF2 is required to maintain stability of E6E7 mRNAs. These data show that SRSF2 is a key regulator of HPV16 oncoprotein expression and cervical tumor maintenance. |
| Used Model | W12ti, 293T, CaSki, and SiHa cells |
| DOI | 10.1128/JVI.03434-14 |
