Poly(A)-binding protein binds to the non-polyadenylated 3' untranslated region of dengue virus and modulates translation efficiency.
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.
Polacek
Charlotta
C
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354, USA.
Friebe
Peter
P
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354, USA.
Harris
Eva
E
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354, USA.
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
D020413:3' Untranslated Regions; D039103:Poly(A)-Binding Protein II; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins