Influence of microRNA on the Maintenance of Human Iron Metabolism

Iron is an essential nutrient critical for many cellular functions including DNA synthesis, ATP generation, and cellular proliferation. Though essential, excessive iron may contribute to the generation of free radicals capable of damaging cellular lipids, proteins, and nucleic acids. As such, the maintenance and control of cellular iron homeostasis is critical to prevent either iron deficiency or iron toxicity conditions. The maintenance of cellular iron homeostasis is largely coordinated by a family of cytosolic RNA binding proteins known as Iron Regulatory Proteins (IRP) that function to post-transcriptionally control the translation and/or stability of mRNA encoding proteins required for iron uptake, storage, transport, and utilization. More recently, a class of small non-coding RNA known as microRNA (miRNA) has also been implicated in the control of iron metabolism. To date, miRNA have been demonstrated to post-transcriptionally regulate the expression of genes associated with iron acquisition (transferrin receptor and divalent metal transporter), iron export (ferroportin), iron storage (ferritin), iron utilization (ISCU), and coordination of systemic iron homeostasis (HFE and hemojevelin). Given the diversity of miRNA and number of potential mRNA targets, characterizing factors that contribute to alterations in miRNA expression, biogenesis, and processing will enhance our understanding of mechanisms by which cells respond to changes in iron demand and/or iron availability to control cellular iron homeostasis.