Regulation of transferrin receptor and ferritin synthesis by iron

Schematic representations of the regulation of transferrin receptor and ferritin synthesis through translational controls operated by the iron-responsive elements (IREs) and the iron regulatory proteins IRP1 and IRP2. Only one IRE is present in the 5'-untranslated region (UTR) of ferritin mRNA, which is shown on the upper two diagrams. When cellular iron is scarce (upper left diagram), iron regulatory protein (IRP) molecules (shown as the pac-man-like circles) 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 IRP2 to the 5' IRE (upper right) and allows efficient mRNA translation to proceed. Five IREs are present in the 3'-UTR of transferrin receptor (TfR) mRNA, shown on the two lower diagrams. When cellular iron is scarce (lower left diagram), binding of IRPs to the IREs in the 3'-UTR stabilizes TfR mRNA and increases TfR translation. Conversely, when iron is abundant (right lower diagram), IREs are not occupied by IRPs, and TfR mRNA is rapidly degraded.