Non-iron metals bind with iron regulatory protein to influence its function

An iron regulatory protein (IRP) is an RNA-binding protein that regulates the expression of several mRNAs such as transferrin receptor (Tf-Rc) and ferritin mRNAs in response to the availability of cellular iron (Fe). IRP interacts with the iron-responsive element (IRE) in both of mRNAs to regulate the life span and to modulate the translation rate of ferritin. IRP was also identified as cytosol aconitase. We previously demonstrated that aluminum (Al) as well as Fe decrease the expression of Tf-Rc mRNA in rat cortical cells treated with Al- and Fe-nitrilotriacetate. In this study, we examined the effect of non-Fe metals on IRP using gel shift and the enzyme assays. IRE was transcriptionally synthesized in vitro and IRP purified from the beef liver. Non-Fe metals including mercury, cadmium, copper, manganese and nickel decreased the binding activities of IRP to IRE with an increase in the aconitase activity in a dose-dependent manner. These data suggest that non-Fe metals bind IRP in 3Fe-4S state to influence its function.