title: Poly(A)-binding protein binds to the non-polyadenylated 3' untranslated region of dengue virus and modulates translation efficiency.
abstract: Poly(A)-binding protein (PABP) is a key player in mRNA circularization and translation initiation of polyadenylated mRNAs. It simultaneously binds the 3' poly(A) tail of an mRNA and eukaryotic initiation factor 4G (eIF4G), which forms part of the translation initiation complex assembling at the 5'end, thus circularizing the RNA molecule and enhancing translation initiation. Here, we report the binding of PABP to the non-polyadenylated 3'end of dengue virus (DENV) RNA. PABP binds the DENV 3' untranslated region (3'UTR) internally, upstream of the conserved 3'stem-loop near the two dumb-bell structures, and can be displaced by poly(A) RNA. The PABP-specific translation inhibitor PABP-interacting protein 2 (Paip2) interferes with the DENV 3'UTR-PABP interaction, and in vitro translation of DENV reporter RNAs in baby hamster kidney cell extracts is inhibited by Paip2 in a dose-dependent manner. Our findings show an expanded translation mechanism for PABP, binding to a viral RNA lacking a terminal poly(A) tail.
authors.affiliation: Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354, USA.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Polacek
authors.affiliation: Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Friebe
authors.affiliation: Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D007668:Kidney / Q000166:cytology / Q000821:virology; D039103:Poly(A)-Binding Protein II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D039103:Poly(A)-Binding Protein II; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins