Iron regulation of ferritin gene expression.
Ferritin is a ubiquitous iron-storage protein found in the cells of animals, plants, molds, and bacteria which it protects from toxic intracellular levels of iron. Ferritin stores iron within a hollow protein shell formed by subunits of two types, H and L. The 5' untranslated regions of the two subunit mRNAs contain an almost identical 28-nucleotide sequence which regulates translation by binding to a specific cell sap protein. When cell iron level is low, this repressor protein obstructs translation of stored ferritin mRNAs, whereas increased iron levels release this protein, thus permitting extensive ferritin subunit synthesis to respond rapidly. Similar motifs in the 3' untranslated region of transferrin receptor mRNA interact with this protein to regulate breakdown of the mRNA and thus change the receptor population. Finally, transcription of the H and L genes can be independently increased by iron and other factors. In the case of iron, synthesis of the L-mRNA is increased preferentially since ferritin shells with a preponderance of L-subunits store iron more efficiently. Thus regulation of ferritin synthesis at the translational and transcriptional levels and by transferrin receptor mRNA abundance at the level of breakdown provide a coordinated mechanism for protecting cells against the effects of excess iron.
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USDA Human Nutrition Research Center on Aging, Tufts, Boston, Massachusetts 02111.
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D035925:Iron-Regulatory Proteins; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron