Ferritin, composed of H-subunits and L-subunits, plays important roles in
iron storage and in the control of intracellular
iron distribution. Synthesis of both subunits is controlled by common cytoplasmic
proteins,
iron regulatory proteins (IRP-1 and IRP-2) that bind to the
iron-responsive
element (IRE) in the 5'-untranslated region of
ferritin messenger RNA (
mRNA). When intracellular
iron is scarce, IRPs display IRE binding to suppress translation of
mRNA. When cellular
iron is abundant, IRPs become inactivated (IRP-1) or degraded (IRP-2). In the last few years, IRE mutations that cause disorders due to dysregulation of
ferritin subunit synthesis have been identified.
Hereditary hyperferritinemia-cataract syndrome is associated with point mutations or deletions in the IRE of L-subunit
mRNA and is characterized by constitutively increased synthesis of L-subunits but is unrelated to
iron overload. A single-point mutation in the IRE of H-subunit
mRNA in members of a family affected with dominantly inherited
iron overload has been reported. This review summarizes the current understanding of the translational disorders caused by IRE mutations in
ferritin mRNA.