2017年5月
Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase- Domain-Containing Protein 3 mRNAs
CELL REPORTS
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- 巻
- 19
- 号
- 8
- 開始ページ
- 1614
- 終了ページ
- 1630
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.celrep.2017.05.009
- 出版者・発行元
- CELL PRESS
Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1(-/-) mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2 alpha suppression. Finally, we show that Regnase-1 is a HIF2 alpha-inducible gene and thus provides a positive feedback loop for HIF2 alpha activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.
- リンク情報
- ID情報
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- DOI : 10.1016/j.celrep.2017.05.009
- ISSN : 2211-1247
- Web of Science ID : WOS:000402125500011