La autoantigen is required for the internal ribosome entry site-mediated translation of Coxsackievirus B3 RNA.
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.
Ray
Partho Sarothi
PS
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.
Das
Saumitra
S
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
D020121:5' Untranslated Regions; D001324:Autoantigens; D034741:RNA, Small Interfering; D012367:RNA, Viral; D012261:Ribonucleoproteins; D000097585:SS-B Antigen