Ferritin Synthesis is Controlled by Iron-Dependent Translational Derepression and by Changes in Synthesis/Transport of Nuclear Ferritin RNAs

Ferritin synthesis, maintained at a very low basal rate when extracellular iron levels are low, is elevated up to 50-fold when iron levels are increased. Previous examinations of this iron-dependent activation have concluded that changes in ferritin synthesis result from selective translational activation conferred by an "iron response element" that lies near the 5' terminus of all known ferritin mRNAs. By placing an iron response element in an optimal position in other mRNAs, we find the iron response element to be a potent translational repressor whose influence can only partially be abrogated under optimal inducing conditions. Further, we show that the 25- to 50-fold iron-mediated increase in ferritin synthesis results from coupling a 5- to 6-fold iron-dependent translational derepression with a similar 5- to 6-fold nuclear-dependent increase in mRNA level.