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10.1016j.celrep.2017.05.009.pdf | 5.65 MB | Adobe PDF | 見る/開く |
タイトル: | Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs |
著者: | Yoshinaga, Masanori Nakatsuka, Yoshinari Vandenbon, Alexis https://orcid.org/0000-0003-2180-5732 (unconfirmed) Ori, Daisuke Uehata, Takuya Tsujimura, Tohru Suzuki, Yutaka Mino, Takashi https://orcid.org/0000-0002-9562-008X (unconfirmed) Takeuchi, Osamu https://orcid.org/0000-0002-1260-6232 (unconfirmed) |
著者名の別形: | 吉永, 正憲 竹内, 理 |
発行日: | 23-May-2017 |
出版者: | Elsevier BV |
誌名: | Cell Reports |
巻: | 19 |
号: | 8 |
開始ページ: | 1614 |
終了ページ: | 1630 |
抄録: | 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 HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. |
記述: | 腸で鉄の吸収を調節するメカニズムの一端を解明 -- 貧血時に鉄吸収を促進するフィードバック機構を発見--. 京都大学プレスリリース. 2017-05-24. |
著作権等: | © 2017 The Authors. This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/224949 |
DOI(出版社版): | 10.1016/j.celrep.2017.05.009 |
PubMed ID: | 28538180 |
関連リンク: | http://www.kyoto-u.ac.jp/ja/research/research_results/2017/170524_1.html |
出現コレクション: | 学術雑誌掲載論文等 |
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