title: A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding.
abstract: The eukaryotic mRNA 3' poly(A) tail and the 5' cap cooperate to synergistically enhance translation. This interaction is mediated by the cap-binding protein eIF4E, the poly(A) binding protein (PABP), and eIF4G, a scaffolding protein that bridges between eIF4E and PABP to bring about the circularization of the mRNA. The translational repressor, Paip2 (PABP-interacting protein 2), inhibits translation by promoting the dissociation of PABP from poly(A). Here we report on the existence of an alternative mechanism by which Paip2 inhibits translation by competing with eIF4G for binding to PABP. We demonstrate that Paip2 can abrogate the translational activity of PABP, which is tethered to the 3' end of the mRNA. Thus, Paip2 can inhibit translation by a previously unrecognized mechanism, which is independent of its ability to disrupt PABP-poly(A) interaction.
authors.affiliation: Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, QC, Canada H3G 1Y6.
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Karim
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: Avak
authors.initials: A
authors.lastname: Kahvejian
authors.forename: Gregory
authors.initials: G
authors.lastname: De Crescenzo
authors.forename: Mauro
authors.initials: M
authors.lastname: Costa-Mattioli
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D002352:Carrier Proteins; D039603:Eukaryotic Initiation Factor-4G; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins