Translational control by iron-responsive elements.

Abstract

In the 1970-ies, Munro and colleagues made the fundamental observation that iron regulates the translation of ferritin mRNA (Z a hringer et al., 1976). Intensive efforts during the past years have allowed to understand the molecular basis of this observation and to extend it to an increasingly well understood picture of how cellular iron homeostasis is maintained. In contrast to most types of gene regulation, all known events involved in the control of cellular iron metabolism occur in the cytoplasm. Specific regulatory elements (called “ironresponsive elements” or “IREs”) are contained within the mRNAs encoding several proteins involved in iron metabolism. A bi-functional cytoplasmic protein (see below) can bind to IREs in an iron-dependent way (Leibold and Munro, 1988) and regulates the translation or the cytoplasmic stability of its target mRNAs. This protein is referred to by different groups as “iron regulatory factor (IRF)”, “IRE-binding protein (IRE-BP)”, “ferritin repressor protein (FRP)” or “p90”.