Schematic model of IRP activity on 5' IREs. IRP1 and IRP2 bind to IRE hairpins under conditions of low iron, thereby inhibiting scanning ribosomes from accessing the start codon. When iron is abundant, IRP1 assembles an Fe-S cluster, converting it to cytoplasmic Aconitase (ACO1) that is unable to bind IREs. IRP2 is degraded in an iron-dependent proteasomal pathway that relies on an iron-sensor F-box protein, FBXL5. After the removal of IRPs from the 5' IRE sequence, ribosomes can translate the coding sequence (CDS).
