The ferritin genes: their response to iron status.
Iron is a required nutrient which, at high concentrations, can peroxidize cell lipids and other cellular components. To prevent excess iron from damaging cells, it is stored in ferritin, which consists of a shell of protein subunits of two related types, H (heavy) and L (light), surrounding a cavity in which the iron can be deposited. In order to prepare for a rapid increase in ferritin in response to a rise in cellular iron, a large number of dormant ferritin mRNAs are accumulated in the cytoplasm. These can be rapidly activated to yield a large population of ferritin subunits. Regulation is achieved through a 28-nucleotide "stem-and-loop" structure near the beginning of the H- and L-ferritin mRNAs. When this structure is associated with a binding protein (iron regulatory element binding protein, IRE-BP), translation of the ferritin mRNA cannot proceed. However, when intracellular iron accumulates, IRE-BP releases its hold and translation of the mRNA then takes place. IRE-BP has been identified as a cytosolic form of aconitase, containing several fourfold iron-sulfur clusters. Within each cluster one iron atom is labile; this may be the mechanism by which IRE-BP responds to intracellular iron levels. Finally, transcription of the L- and H-genes shows that L is preferentially transcribed in response to increased iron intake, whereas H responds to cell differentiation and other factors. More work is needed to define independent transcription of the individual genes, including regulation of components other than the 28-nucleotide segment.
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USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
D000818:Animals; D001483:Base Sequence; D005293:Ferritins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology
D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005293:Ferritins; D007501:Iron