title: Translational repression by a novel partner of human poly(A) binding protein, Paip2.
abstract: The eukaryotic mRNA 3' poly(A) tail acts synergistically with the 5' cap structure to enhance translation. This effect is mediated by a bridging complex, composed of the poly(A) binding protein (PABP), eIF4G, and the cap binding protein, eIF4E. PABP-interacting protein 1 (Paip1) is another factor that interacts with PABP to coactivate translation. Here, we describe a novel human PABP-interacting protein (Paip2), which acts as a repressor of translation both in vitro and in vivo. Paip2 preferentially inhibits translation of a poly(A)-containing mRNA, but has no effect on the translation of hepatitis C virus mRNA, which is cap- and eIF4G-independent. Paip2 decreases the affinity of PABP for polyadenylate RNA, and disrupts the repeating structure of poly(A) ribonucleoprotein. Furthermore, Paip2 competes with Paip1 for PABP binding. Thus, Paip2 inhibits translation by interdicting PABP function.
authors.affiliation: Department of Biochemistry, McGill Cancer Center, McGill University, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: K
authors.initials: K
authors.lastname: Khaleghpour
authors.forename: Y V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: A W
authors.initials: AW
authors.lastname: Craig
authors.forename: C T
authors.initials: CT
authors.lastname: DeMaria
authors.forename: R C
authors.initials: RC
authors.lastname: Deo
authors.forename: S K
authors.initials: SK
authors.lastname: Burley
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000235:genetics; D015153:Blotting, Western; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011817:Rabbits; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018387:Codon, Initiator; C111580:PAIP1 protein, human; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins