Iron regulatory proteins 1 and 2

Abstract

Iron uptake and storage in mammalian cells is at least partly regulated at a post-transcriptional level by the iron regulatory proteins (IRP-1 and IRP-2). These cytoplasmic regulators share 79% similarity in protein sequence and bind tightly to conserved mRNA stem-loops, named iron-responsive elements (IREs). The IRP:IRE interaction underlies the regulation of translation and stability of several mRNAs central to iron metabolism. The question of why the cell requires two such closely related regulatory proteins may be resolved as we learn more about the expression and regulation of these proteins. It is evident so far that, despite similarities, the IRPs differ in several important respects. They are coordinately regulated by cellular iron, but whereas IRP-1 is inactivated by high iron levels, IRP-2 is rapidly degraded. Further differences arise in their expression and RNA-binding specificity. The two proteins each recognise a large repertoire of IRE-like sequences, including a small group of exclusive RNA targets. These findings hint that IRP-1 and IRP-2 may bind preferentially to certain mRNAs in vivo, possibly extending their known functions beyond the regulation of intracellular iron homeostasis.