Iron regulatory elements (IREs): a family of mRNA non-coding sequences

and metal regulatory elements (Silver and Walderhaugh, 1992).In eukaryotic mRNAs, IREs (Iron Regulatory Elements) are the only characterized family of cis (non-coding) regulatory elements (reviewed in Theil, 1990Theil, ,1993;;Klausner et al., 1993).IREs appear to be composites of an iron-specific regulatory element fused to either a generic translation control element or mRNA stability element (Figure la).When cellular iron concentrations are low, ferritin mRNA is not translated (Zahringer et al., 1976; Schaefer and Theil, 1981; Shull and Theil, 1982).At the same time, the transferrin receptor (TfR) mRNA is stabilized and translated (Mullner and Kuhn, 1988).Thus when no iron is available to concentrate or to store, the cell is spared the expense of synthesizing ferritin and TfR synthesis allows iron uptake.When iron levels are high, ferritin mRNA is translated and TfR mRNA is degraded, allowing iron storage and preventing iron uptake.Co-ordinated regulation of iron storage and iron uptake depends on the interaction of a protein regulator, the iron regulatory protein (IRP), and the IRE family of mRNA sequences (Aziz and Munro, 1987;