IDENTIFICATION OF A CONSERVED AND FUNCTIONAL IRON-RESPONSIVE ELEMENT IN THE 5'-UNTRANSLATED REGION OF MAMMALIAN MITOCHONDRIAL ACONITASE

Iron responsive elements (IREs) are RNA stem-loop motifs found in gene s of iron metabolism. When cells are iron depleted, iron regulatory pr oteins (IRPs) bind to IREs in the transcripts of ferritin, transferrin receptor, and erythroid amino-levulinic acid synthetase. Binding of I RPs to IRE motifs near the 5' end of the transcript results in attenua tion of translation while binding to IREs in the 3'-untranslated regio n of the transferrin receptor results in protection from endonucleolyt ic cleavage. Iron deprivation results in activation of IRE binding act ivity, whereas iron replete cells lose IRE binding activation. Here, w e report the identification of a conserved IRE in the 5'-untranslated region of the transcript of the citric acid cycle enzyme mitochondrial aconitase from four different mammalian species. The IRE in the trans cript of mitochondrial aconitase can mediate in vitro translational re pression of mitochondrial aconitase by IRPs. Furthermore, levels of mi tochondrial aconitase are decreased in mice maintained on a low iron d iet, whereas levels of mRNA remain unchanged. The decrease in levels o f mitochondrial aconitase is likely due to activation of IRP binding a nd consequent attenuation of translation. Thus, expression of the iron -sulfur protein mitochondrial aconitase and function of the citric aci d cycle may be regulated by iron levels in cells.