Eukaryotic translation initiation factor 4AIII (eTF4AIII) is functionally distinct from eIF4AI and eIF4AII

Eukaryotic initiation factor 4A (eIF4A) is an RNA-dependent ATPase and ATP- dependent RNA helicase that is thought to melt the 5' proximal secondary st ructure of eukaryotic mRNAs to facilitate attachment of the 40S ribosomal s ubunit. eIF4A functions in a complex termed eIF4F with two other initiation factors (eIF4E and eIE4G). Two isoforms of eIF4A, eIF4AI and eIF4AII, whic h are encoded by two different genes, are functionally indistinguishable, A third member of the eIF4A family, eIF4AIII, whose human homolog exhibits 6 5% amino acid identity to human eIF4AI, has also been cloned from Xenopus a nd tobacco, but its function in translation has not been characterized. In this study, human eIF4AIII was characterized biochemically. While eIF4AIII, like eIF4AI, exhibits RNA-dependent ATPase activity and ATP-dependent RNA helicase activity, it fails to substitute for eIF4AI in an in vitro-reconst ituted 40S ribosome binding assay. Instead, eIF4AIII inhibits translation i n a reticulocyte lysate system. In addition, whereas eIF4AI binds independe ntly to the middle and carboxy-terminal fragments of eIF4G, eIF4AIII binds to the middle fragment only. These functional differences between eIF4AI an d eIF4AIII suggest that eIF4AIII might play an inhibitory role in translati on under physiological conditions.