Translational regulation of ferritin synthesis, which applies to both the H and L subunit. (A) A single functional IRE is found in the 5′ UTR of the genes encoding ferritin H and L subunits, and this noncoding sequence behaves as an mRNA cis-acting element. The other component of this regulatory system is a specific trans-acting cytoplasmic binding protein, called iron regulatory protein (IRP; two IRPs, IRP-1 and IRP-2, have been identified so far). When cellular iron is scarce, IRP binds to IRE, where it inhibits ferritin translation. When cellular iron is abundant, formation of [4Fe-4S] clusters within IRP prevents binding to IRE; as a consequence, ferritin synthesis is allowed. The reader is referred to the comprehensive review by Klausner et al8 for details. (B) Sequence and proposed structure of ferritin L-subunit IRE. The reader is referred to the comprehensive review by Theil9 for details. The IRE bulge has been depicted according to Butt et al.10