title: Poly(A) binding protein 1 enhances cap-independent translation initiation of neurovirulence factor from avian herpesvirus.
abstract: Poly(A) binding protein 1 (PABP1) plays a central role in mRNA translation and stability and is a target by many viruses in diverse manners. We report a novel viral translational control strategy involving the recruitment of PABP1 to the 5' leader internal ribosome entry site (5L IRES) of an immediate-early (IE) bicistronic mRNA that encodes the neurovirulence protein (pp14) from the avian herpesvirus Marek's disease virus serotype 1 (MDV1). We provide evidence for the interaction between an internal poly(A) sequence within the 5L IRES and PABP1 which may occur concomitantly with the recruitment of PABP1 to the poly(A) tail. RNA interference and reverse genetic mutagenesis results show that a subset of virally encoded-microRNAs (miRNAs) targets the inhibitor of PABP1, known as paip2, and therefore plays an indirect role in PABP1 recruitment strategy by increasing the available pool of active PABP1. We propose a model that may offer a mechanistic explanation for the cap-independent enhancement of the activity of the 5L IRES by recruitment of a bona fide initiation protein to the 5' end of the message and that is, from the affinity binding data, still compatible with the formation of 'closed loop' structure of mRNA.
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, United Kingdom.
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Tahiri-Alaoui
authors.affiliation: The Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, United Kingdom.
authors.forename: Yashar
authors.initials: Y
authors.lastname: Sadigh
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Popplestone
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, United Kingdom.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kgosana
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, United Kingdom.
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Smith
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, United Kingdom.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Nair
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D005786:Gene Expression Regulation; D008381:Herpesvirus 2, Gallid / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010442:Peptide Chain Initiation, Translational; D011061:Poly A / Q000235:genetics / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D037521:Virulence Factors; D011061:Poly A