Translation driven by an eIF4G core domain in vivo

Most eukaryotic mRNAs possess a 5' cap structure (m(7)GpppN) and a 3' poly( A) tail which promote translation initiation by binding the eukaryotic tran slation initiation factor (eIF)4E and the poly(A) binding protein (PABP), r espectively. eIF4G can bridge between eIF4E and PABP, and-through eIF3-is t hought to establish a link to the small ribosomal subunit. We fused the C-t erminal region of human eIF4GI lacking both the eIF4E- and PABP-binding sit es, to the IRE binding protein IRP-1, This chimeric protein suffices to dir ect the translation of the downstream cistron of bicistronic mRNAs bearing IREs in their intercistronic space in vivo. This function is preserved even when translation via the 5' end is inhibited. Deletion analysis defined th e conserved central domain (amino acids 642-1091) of eIF4G as an autonomous 'ribosome recruitment core' and implicated eIF4A as a critical binding par tner. Our data reveal the sufficiency of the conserved eIF4G ribosome recru itment core to drive productive mRNA translation in living cells. The C-ter minal third of eIF4G is dispensable, and may serve as a regulatory domain.