Coordinate regulation of transferrin receptor and ferritin synthesis through translational controls operated by the iron-responsive elements (IREs) and by the iron regulatory proteins IRP1 and IRP2.

Only one IRE is present in the 5′-UTR of ferritin mRNA. When cellular iron is scarce, IRP molecules are available for binding the 5′ IRE; initiation of translation is prevented; and ferritin synthesis is inhibited. By contrast, presence of abundant intracellular iron prevents binding of IRPs to the 5′ IRE and allows efficient mRNA translation to proceed (green arrow). Five IREs are present in the 3′-UTR of transferrin receptor (TfR) mRNA. When cellular iron is scarce, binding of one or more IRPs to the IREs in the 3′-UTR stabilizes TfR mRNA and increases TfR translation. Conversely, when iron is abundant, very few IREs are occupied by IRPs, and TfR mRNA is rapidly degraded. Adapted from Brittenham GM, Olivieri NF, Rouault TA. Iron physiology and iron overload. Hematology 1996. The American Society of Hematology, Orlando, FL, 1996, p. 177.