title: La autoantigen is required for the internal ribosome entry site-mediated translation of Coxsackievirus B3 RNA.
abstract: Translation initiation in Coxsackievirus B3 (CVB3) occurs via ribosome binding to an internal ribosome entry site (IRES) located in the 5'-untranslated region (UTR) of the viral RNA. This unique mechanism of translation initiation requires various trans-acting factors from the host. We show that human La autoantigen (La) binds to the CVB3 5'-UTR and also demonstrate the dose-dependent effect of exogenously added La protein in stimulating CVB3 IRES-mediated translation. The requirement of La for CVB3 IRES mediated translation has been further demonstrated by inhibition of translation as a result of sequestering La and its restoration by exogenous addition of recombinant La protein. The abundance of La protein in various mouse tissue extracts has been probed using anti-La antibody. Pancreatic tissue, a target organ for CVB3 infection, was found to have a large abundance of La protein which was demonstrated to interact with the CVB3 5'-UTR. Furthermore, exogenous addition of pancreas extract to in vitro translation reactions resulted in a dose dependent stimulation of CVB3 IRES-mediated translation. These observations indicate the role of La in CVB3 IRES-mediated translation, and suggest its possible involvement in the efficient translation of the viral RNA in the pancreas.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.
authors.forename: Partho Sarothi
authors.initials: PS
authors.lastname: Ray
authors.forename: Saumitra
authors.initials: S
authors.lastname: Das
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001324:Autoantigens; D001665:Binding Sites; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D029822:Enterovirus B, Human / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010179:Pancreas / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000494:pharmacology / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D014018:Tissue Distribution; D000097585:SS-B Antigen
chemical_list: D020121:5' Untranslated Regions; D001324:Autoantigens; D034741:RNA, Small Interfering; D012367:RNA, Viral; D012261:Ribonucleoproteins; D000097585:SS-B Antigen