Gene Regulation

12_GeneReg

Eukaryotic mRNA Processing

Splicing of mRNA

RNA Binding Proteins

Iron Response Elements

Iron Response Elements (IREs) are stem-loop structures found in UTRs of mRNAs involved in iron metabolism, like Ferritin and Transferrin. IREs are bound by Iron Regulatory Proteins (IRPs) and act as sensors of iron. In the absence of Iron, IRP1 binds to IREs. In the presence of Iron, IRP1 releases from the mRNA.

RF00037 Iron Response Element
The predicted secondary structure of Iron Response Element (IRE) sequences in mRNA with level of conservation color coded. Credit: Whidou (CC-BY-SA 4.9)
FeRegulatoryProtein.pdb
Three dimensional model of Iron Regulatory Protein 1 (IRP1) bound to and IRE. Credit: Jmol development team (GNU GPL)

IRP1 is bifunctional in regulating the translation of Transferrin and Ferritin based on the location with UTRs and proximity to destabilization sequences. In the case of Ferritin (a cytosolic iron storage protein), Iron presence releases IRP1 binding to the 5′-UTR to enable active translation of this stored mRNA. In the case of Transferrin (a facilitator of iron transport into the cell), Iron also releases IRP1 binding to it’s mRNA (in the 3′-UTR), but exposes destabilization sequences that results in rapid degradation of the mRNA.