Figure 4.

Regulation of ferritin and TfR1 by IRP1. In the absence of iron, IRP1 without an [4Fe-4S] cluster binds the 5′-IRE of ferritin mRNA, which sterically blocks the translation of ferritin. However, in the presence of high iron concentrations, IRP1 cannot bind to the 5′ IRE of ferritin mRNA due to the formation of a [4Fe-4S] cluster, and translation is active. On the other hand, when IRPs bind the 3′-IREs of TfR1 mRNA, this interaction stabilizes the mRNA and protects it from endonucleases so that TfR1 translation can occur. Whereas, under high iron concentrations, IRPs cannot bind to the 3′-IREs of the TfR1, and the mRNA is exposed and degraded by endonucleases.