Iron-regulatory proteins limit hypoxia-inducible factor 2α expression in iron deficiency
Author
Sanchez, Mayka
Galy, Bruno
Muckenthaler, Martina U.
Hentze, Matthias W.
Publication date
2007ISSN
1545-9993
Abstract
Hypoxia stimulates erythropoiesis, the major iron-utilization pathway. We report the discovery of a conserved, functional iron-responsive element (IRE) in the 5′ untranslated region of the messenger RNA encoding endothelial PAS domain protein-1, EPAS1 (also called hypoxia-inducible factor-2α, HIF2α). Via this IRE, iron regulatory protein binding controls EPAS1 mRNA translation in response to cellular iron availability. Our results uncover a regulatory link that permits feedback control between iron availability and the expression of a key transcription factor promoting iron utilization. They also show that an IRE that is structurally distinct from, for example, the ferritin mRNA IRE and that has been missed by in silico approaches, can mediate mechanistically similar responses.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Medicina
Medicina
Medicine
Pages
6
Publisher
Springer Nature
Collection
14
Is part of
Nature Structural & Molecular Biology
Citation
Sanchez, Mayka; Galy, Bruno; Muckenthaler, Martina U. [et al.]. Iron-regulatory proteins limit hypoxia-inducible factor-2α expression in iron deficiency. Nature Structural & Molecular Biology, 2007, 14, p. 420–426. Disponible en: <https://www.nature.com/articles/nsmb1222>. Fecha de acceso: 22 ene. 2024. DOI: 10.1038/nsmb1222
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- Ciències de la Salut [732]