IRP-1 BINDING TO FERRITIN MESSENGER-RNA PREVENTS THE RECRUITMENT OF THE SMALL RIBOSOMAL-SUBUNIT BY THE CAP-BINDING COMPLEX ELF4F

Binding of iron regulatory proteins (IRPs) to IREs located in proximit y to the cap structure of ferritin H- and L-chain mRNAs blocks ferriti n synthesis by preventing the recruitment of the small ribosomal subun it to the mRNA. We have devised a novel procedure to examine the assem bly of translation initiation factors (eIFs) on regulated mRNAs. Unexp ectedly, we find that the cap binding complex eIF4F (comprising eIF4E, eIF4G, and eIF4A) assembles even when IRP-1 is bound to the cap-proxi mal IRE. This assembly is futile, because bridging interactions betwee n eIF4F and the small ribosomal subunit cannot be established in the p resence of IRP-1. Our findings provide insight into translational cont rol by an mRNA binding protein at the level of translation initiation factors and uncover a key regulatory step in iron homeostasis.