eIF4G functionally differs from eIFiso4G in promoting internal initiation,cap-independent translation, and translation of structured mRNAs

Eukaryotic initiation factor (eIF) 4G plays an important role in assembling the initiation complex required for ribosome binding to an mRNA. Plants, a nimals, and yeast each express two eIF4G homologs, which share only 30, 46, and 53% identity, respectively. We have examined the functional difference s between plant eIF4G proteins, referred to as eIF4G and eIFiso4G, when pre sent as subunits of eIF4F and eIFiso4F, respectively. The degree to which a 5'-cap stimulated translation was inversely correlated with the concentrat ion of eIF4F or eIFiso4F and required the poly(A)-binding protein for optim al function. Although eIF4F and eIFiso4F directed translation of unstructur ed mRNAs, eIF4F supported translation of an mRNA containing 5'-proximal sec ondary structure substantially better than did eIFiso4F. Moreover, eIF4F st imulated translation from uncapped monocistronic or dicistronic mRNAs to a greater extent than did eIFiso4F. These data suggest that at least some fun ctions of plant eIFiso4F and eIF4F have diverged in that eIFiso4F promotes translation preferentially from unstructured mRNAs, whereas eIF4F can promo te translation also from mRNAs that contain a structured 5'-leader and that are uncapped or contain multiple cistrons. This ability may also enable eI F4F to promote translation from standard mRNAs under cellular conditions in which cap-dependent translation is inhibited.