title: General RNA-binding proteins have a function in poly(A)-binding protein-dependent translation.
abstract: The interaction between the poly(A)-binding protein (PABP) and eukaryotic translational initiation factor 4G (eIF4G), which brings about circularization of the mRNA, stimulates translation. General RNA-binding proteins affect translation, but their role in mRNA circularization has not been studied before. Here, we demonstrate that the major mRNA ribonucleoprotein YB-1 has a pivotal function in the regulation of eIF4F activity by PABP. In cell extracts, the addition of YB-1 exacerbated the inhibition of 80S ribosome initiation complex formation by PABP depletion. Rabbit reticulocyte lysate in which PABP weakly stimulates translation is rendered PABP-dependent after the addition of YB-1. In this system, eIF4E binding to the cap structure is inhibited by YB-1 and stimulated by a nonspecific RNA. Significantly, adding PABP back to the depleted lysate stimulated eIF4E binding to the cap structure more potently if this binding had been downregulated by YB-1. Conversely, adding nonspecific RNA abrogated PABP stimulation of eIF4E binding. These data strongly suggest that competition between YB-1 and eIF4G for mRNA binding is required for efficient stimulation of eIF4F activity by PABP.
authors.affiliation: Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Evdokimova
authors.forename: Ann
authors.initials: A
authors.lastname: Brasey
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Pestova
authors.forename: Daniel
authors.initials: D
authors.lastname: Fantus
authors.forename: Akiko
authors.initials: A
authors.lastname: Yanagiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Imataka
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Skabkin
authors.forename: Lev P
authors.initials: LP
authors.lastname: Ovchinnikov
authors.forename: William C
authors.initials: WC
authors.lastname: Merrick
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D002457:Cell Extracts; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D011817:Rabbits; D051840:Y-Box-Binding Protein 1
chemical_list: D002457:Cell Extracts; D004268:DNA-Binding Proteins; D039562:Eukaryotic Initiation Factor-4F; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human