title: Far upstream element binding protein 2 interacts with enterovirus 71 internal ribosomal entry site and negatively regulates viral translation.
abstract: An internal ribosomal entry site (IRES) that directs the initiation of viral protein translation is a potential drug target for enterovirus 71 (EV71). Regulation of internal initiation requires the interaction of IRES trans-acting factors (ITAFs) with the internal ribosomal entry site. Biotinylated RNA-affinity chromatography and proteomic approaches were employed to identify far upstream element (FUSE) binding protein 2 (FBP2) as an ITAF for EV71. The interactions of FBP2 with EV71 IRES were confirmed by competition assay and by mapping the association sites in both viral IRES and FBP2 protein. During EV71 infection, FBP2 was enriched in cytoplasm where viral replication occurs, whereas FBP2 was localized in the nucleus in mock-infected cells. The synthesis of viral proteins increased in FBP2-knockdown cells that were infected by EV71. IRES activity in FBP2-knockdown cells exceeded that in the negative control (NC) siRNA-treated cells. On the other hand, IRES activity decreased when FBP2 was over-expressed in the cells. Results of this study suggest that FBP2 is a novel ITAF that interacts with EV71 IRES and negatively regulates viral translation.
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Lin
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Li
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D020121:5' Untranslated Regions; D001665:Binding Sites; D002451:Cell Compartmentation; D045744:Cell Line, Tumor; D029821:Enterovirus A, Human / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006801:Humans; D014176:Protein Biosynthesis; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015534:Trans-Activators / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D020121:5' Untranslated Regions; C105789:KHSRP protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins