title: A novel functional human eukaryotic translation initiation factor 4G.
abstract: Mammalian eukaryotic translation initiation factor 4F (eIF4F) is a cap-binding protein complex consisting of three subunits: eIF4E, eIF4A, and eIF4G. In yeast and plants, two related eIF4G species are encoded by two different genes. To date, however, only one functional eIF4G polypeptide, referred to here as eIF4GI, has been identified in mammals. Here we describe the discovery and functional characterization of a closely related homolog, referred to as eIF4GII. eIF4GI and eIF4GII share 46% identity at the amino acid level and possess an overall similarity of 56%. The homology is particularly high in certain regions of the central and carboxy portions, while the amino-terminal regions are more divergent. Far-Western analysis and coimmunoprecipitation experiments were used to demonstrate that eIF4GII directly interacts with eIF4E, eIF4A, and eIF3. eIF4GII, like eIF4GI, is also cleaved upon picornavirus infection. eIF4GII restores cap-dependent translation in a reticulocyte lysate which had been pretreated with rhinovirus 2A to cleave endogenous eIF4G. Finally, eIF4GII exists as a complex with eIF4E in HeLa cells, because eIF4GII and eIF4E can be purified together by cap affinity chromatography. Taken together, our findings indicate that eIF4GII is a functional homolog of eIF4GI. These results may have important implications for the understanding of the mechanism of shutoff of host protein synthesis following picornavirus infection.
authors.affiliation: Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Gradi
authors.forename: H
authors.initials: H
authors.lastname: Imataka
authors.forename: Y V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: E
authors.initials: E
authors.lastname: Rom
authors.forename: B
authors.initials: B
authors.lastname: Raught
authors.forename: S
authors.initials: S
authors.lastname: Morino
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D006801:Humans; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000302:isolation & purification; D014176:Protein Biosynthesis; D016415:Sequence Alignment
chemical_list: C491300:EIF4G2 protein, human; D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors