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.