Kim H Y, LaVaute T, Iwai K, Klausner R D, Rouault T A
Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1996 Sep 27;271(39):24226-30. doi: 10.1074/jbc.271.39.24226.
Iron-responsive elements (IREs) are RNA stem-loop motifs found in genes of iron metabolism. When cells are iron-depleted, iron regulatory proteins (IRPs) bind to IREs in the transcripts of ferritin, transferrin receptor, and erythroid amino-levulinic acid synthetase. Binding of IRPs to IRE motifs near the 5' end of the transcript results in attenuation of translation while binding to IREs in the 3'-untranslated region of the transferrin receptor results in protection from endonucleolytic cleavage. Iron deprivation results in activation of IRE binding activity, whereas iron replete cells lose IRE binding activation. Here, we 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 transcript of mitochondrial aconitase can mediate in vitro translational repression of mitochondrial aconitase by IRPs. Furthermore, levels of mitochondrial aconitase are decreased in mice maintained on a low iron diet, whereas levels of mRNA remain unchanged. The decrease in levels of mitochondrial aconitase is likely due to activation of IRP binding and consequent attenuation of translation. Thus, expression of the iron-sulfur protein mitochondrial aconitase and function of the citric acid cycle may be regulated by iron levels in cells.
铁反应元件（IREs）是在铁代谢基因中发现的RNA茎环基序。当细胞缺铁时，铁调节蛋白（IRPs）会与铁蛋白、转铁蛋白受体和红细胞δ-氨基乙酰丙酸合成酶转录本中的IREs结合。IRPs与转录本5'端附近的IRE基序结合会导致翻译减弱，而与转铁蛋白受体3'-非翻译区的IREs结合则可保护其免受核酸内切酶切割。缺铁会导致IRE结合活性激活，而铁充足的细胞则会失去IRE结合激活。在此，我们报告在四种不同哺乳动物物种的柠檬酸循环酶线粒体顺乌头酸酶转录本的5'-非翻译区鉴定出一个保守的IRE。线粒体顺乌头酸酶转录本中的IRE可在体外介导IRPs对线粒体顺乌头酸酶的翻译抑制。此外，低铁饮食喂养的小鼠中线粒体顺乌头酸酶水平降低，而mRNA水平保持不变。线粒体顺乌头酸酶水平的降低可能是由于IRP结合激活以及随之而来的翻译减弱。因此，铁硫蛋白线粒体顺乌头酸酶的表达和柠檬酸循环的功能可能受细胞内铁水平的调节。
