| First Author | Yoshinaga M | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 8 | Pages | 1614-1630 |
| PubMed ID | 28538180 | Mgi Jnum | J:254708 |
| Mgi Id | MGI:6103852 | Doi | 10.1016/j.celrep.2017.05.009 |
| Citation | Yoshinaga M, et al. (2017) Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs. Cell Rep 19(8):1614-1630 |
| abstractText | 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 HIF2alpha suppression. Finally, we show that Regnase-1 is a HIF2alpha-inducible gene and thus provides a positive feedback loop for HIF2alpha activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. |
