{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:53:22Z","timestamp":1790837602242,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1992,12,15]]},"abstract":"<jats:p>The translation of ferritin mRNA and degradation of transferrin receptor mRNA are regulated by the interaction of an RNA-binding protein, the iron-responsive element binding protein (IRE-BP), with RNA stem-loop structures known as iron-responsive elements (IREs) contained within these transcripts. IRE-BP produced in iron-replete cells has aconitase (EC 4.2.1.3) activity. The protein shows extensive sequence homology with mitochondrial aconitase, and sequences of peptides prepared from cytosolic aconitase are identical with peptides of IRE-BP. As an active aconitase, IRE-BP is expected to have an Fe-S cluster, in analogy to other aconitases. This Fe-S cluster has been implicated as the region of the protein that senses intracellular iron levels and accordingly modifies the ability of the IRE-BP to interact with IREs. Expression of the IRE-BP in cultured cells has revealed that the IRE-BP functions either as an active aconitase, when the cells are iron-replete, or as an active RNA-binding protein, when the cells are iron-depleted. We compare properties of purified authentic cytosolic aconitase from beef liver with those of IRE-BP from tissue culture cells and establish that characteristics of the physiologically relevant form of the protein from iron-depleted cells resemble those of cytosolic aconitase apoprotein. We demonstrate that loss of the labile fourth iron atom of the Fe-S cluster results in loss of aconitase activity, but that more extensive cluster alteration is required before the IRE-BP acquires the capacity to bind RNA with the affinity seen in vivo. These results are consistent with a model in which the cubane Fe-S cluster is disassembled when intracellular iron is depleted.<\/jats:p>","DOI":"10.1073\/pnas.89.24.11735","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:14:57Z","timestamp":1149063297000},"page":"11735-11739","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":254,"title":["Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding."],"prefix":"10.1073","volume":"89","author":[{"given":"D J","family":"Haile","sequence":"first","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T A","family":"Rouault","sequence":"additional","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J B","family":"Harford","sequence":"additional","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M C","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G A","family":"Blondin","sequence":"additional","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Beinert","sequence":"additional","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R D","family":"Klausner","sequence":"additional","affiliation":[{"name":"Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1992,12,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.89.24.11735","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:31:47Z","timestamp":1649856707000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.89.24.11735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,12,15]]},"references-count":0,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1992,12,15]]}},"alternative-id":["10.1073\/pnas.89.24.11735"],"URL":"https:\/\/doi.org\/10.1073\/pnas.89.24.11735","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,12,15]]},"assertion":[{"value":"1992-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}