Figure 4.

Recruiting unused ferritin mRNA for protein synthesis to minimize hemosiderin formation in iron overload: targeting three-dimensional properties of the IRE-RNA. During iron overload, iron increases inside each ferritin protein cage leading to ferritin damage and hemosiderin formation. Some of the mRNA remains bound to repressor¹⁴ (top). Approximately 50% ferritin IRE-mRNA is still repressed when iron is in excess. Physical studies of the RNA show the IRE structure is a target that binds metals⁹ and is recognized by small organic–metal complexes in living cells (bottom right panel). Figure taken from Ke et al.,¹⁵ allowing drug design that uses the principles of protein drug discovery to exploit the smaller target size of mRNA and addition information of three-dimensional information, contrasting with the limited two-dimensional structure information of and avoiding cells responses to siRNA. Crystals: structure from reference¹⁶ shows exposed IRE-RNA — RNA; — protein; Solution: ■, metal sites from chemical nuclease and NMR analyses.^17,19.26