This project is aimed towards a molecular understanding of the basis of intracellular iron metabolism. A molecular genetic examination of human ferritin has set the basis for defining a cis/trans regulatory model for the post-transcriptional regulation of this critical protein of intracellular iron metabolism. Iron regulates the translation of the mRNA encoding ferritin by virtue of its ability to alter the binding activity of a cytosolic protein that binds to a specific RNA sequence contained within the ferritin message. A complete description of this RNA regulatory element, the RNA binding protein, and how iron regulates their interaction will provide the first complete description of a translational control system in higher eukaryotic cells. In order to elucidate previously unknown components of the human cellular iron metabolism, we have established the mechanism for the uptake of iron in the genetically manipulatable simple eukaryote, Saccharomyces cerevisiae. This has led to the identification of a reductase/transporter system to explain the transmembrane, regulated uptake of iron in this organism.
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