title: eIF4G is required for the pioneer round of translation in mammalian cells.
abstract: Nonsense-mediated mRNA decay (NMD) in mammalian cells targets cap-binding protein 80 (CBP80)-bound mRNA during or after a pioneer round of translation. It is unknown whether eukaryotic translation initiation factor 4G (eIF4G) functions in the pioneer round. We show that baculovirus-produced CBP80 and CBP20 independently interact with eIF4GI. The interactions between eIF4G and the heterodimer CBP80/20 suggest that eIF4G has a function in the pioneer initiation complex rather than merely a presence during remodeling to the steady-state complex. First, NMD is inhibited upon eIF4G cleavage by HIV-2 or poliovirus 2A protease. Second, eIF4GI coimmunopurifies with pre-mRNA, indicating that it associates with transcripts before the pioneer round. Third, eIF4G immunopurifies with Upf NMD factors and eIF4AIII, which are constituents of the pioneer translation initiation complex. We propose a model in which eIF4G serves to connect CBP80/20 with other initiation factors during the pioneer round of translation.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, New York, 14642 USA.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lejeune
authors.forename: Aparna C
authors.initials: AC
authors.lastname: Ranganathan
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Maquat
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D017931:DNA Primers; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger