| Gene Name | U2SURP |
| HF Protein Name | U2 snRNP-associated SURP motif-containing protein |
| HF Function | Host Restriction Factor |
| Uniprot ID | O15042 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 23350 |
| Host Factor (HF) Name in Paper | U2 snRNP |
| Gene synonyms | KIAA0332 SR140 |
| Ensemble Gene ID | ENSG00000163714 |
| Ensemble Transcript | ENST00000473835 [O15042-1] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000398, GO:0003723, GO:0005634, GO:0005654, |
| MINT ID | O15042 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 617849 |
| PANTHER ID | N.A. |
| PDB ID(s) | N.A., |
| pfam ID | PF08312, PF00076, PF01805, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Human adenovirus 3 |
| Virus Short Name | HAdV-5 |
| Order | Unassigned |
| Virus Family | Adenoviridae |
| Virus Subfamily | N.A. |
| Genus | Mastadenovirus |
| Species | Human mastadenovirus C |
| Host | Human, mammals |
| Cell Tropism | Epithelial cells |
| Associated Disease | Very common human infection, estimated to be responsible for between 2% and 5% of all respiratory infections. usually mild respiratory, gastrointestinal and eye infections. |
| Mode of Transmission | Respiratory, fecal-oral |
| VIPR DB link | N.A. |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/93/adenoviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Adenoviridae |
| Paper Title | An siRNA screen identifies the U2 snRNP spliceosome as a host restriction factor for recombinant adeno-associated viruses |
| Author's Name | Claire A. Schreiber, Toshie Sakuma, Yoshihiro Izumiya, Sara J. Holditch, RaymondD. Hickey, Robert K. Bressin, Upamanyu Basu, Kazunori Koide, Aravind Asokan,Yasuhiro Ikeda |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 26244496 |
| Abstract | Adeno-associated viruses (AAV) have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors. |
| Used Model | Hela, 293T and A375 cells |
| DOI | 10.1371/journal.ppat.1005082 |
