The molecular biology of intracellular iron metabolism has been studied by examining the regulation and expression of the gene for human ferritin. Ferritin functions to store, detoxify and regulate intracellular iron. It performs all of these functions via its ability to accumulate large amounts of iron within a 24 subunit shell. The critical determinant of the effect of ferritin upon the cell is its concentration. This is determined by both the level of expression of the 2 subunits not mentioned encoding ferritin and, by iron, through the level of biosynthesis of the protein. We have isolated the gene for human ferritin H chain and have analyzed the molecular basis for the regulation of ferritin biosynthesis by iron. We have demonstrated that a 26 nucleotide region of RNA contained within the 5' untranslated region of ferritin mRNA is only responsible for iron dependent regulation of translation. We have analyzed this RNA element and have referred to it as an iron-responsive element (IRE). We have identified this element as the only element involved in translational control in response to iron. We have identified a cytoplasmic factor or factors which interact specifically with this element and are likely responsible for the iron-dependent translational regulation. In addition, we have begun to examine the molecular basis of iron metabolism in the yeast Saccharomyces cerevisiae in order to illuminate the genes in this primitive eukaryote involved in iron metabolism.
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