Iron-responsive elements (IREs) are regulatory RNA elements which serve as specific binding sites for the IRE-binding protein (IRE-BP). Interaction between IREs and IRE-BP induces repression of ferritin mRNA translation and transferrin receptor mRNA stabilization. We describe the identification of extensive amino acid sequence homology between IRE-BP and two known isomerases, aconitase and isopropylmalate (IPM) isomerase. We discuss the implications of this observation with regard to structure/function relationships of IRE-BP. The structural conservation between a regulatory RNA-binding protein and two enzymes involved in intermediary metabolism provides a surprising example of the functional flexibility in biological structures.