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j.celrep.2023.112157.pdf | 4.24 MB | Adobe PDF | 見る/開く |
タイトル: | Minimal upstream open reading frame of Per2 mediates phase fitness of the circadian clock to day/night physiological body temperature rhythm |
著者: | Miyake, Takahito https://orcid.org/0000-0002-4356-5883 (unconfirmed) Inoue, Yuichi Shao, Xinyan Seta, Takehito Aoki, Yuto Nguyen Pham, Khanh Tien Shichino, Yuichi Sasaki, Junko Sasaki, Takehiko Ikawa, Masahito Yamaguchi, Yoshiaki Okamura, Hitoshi Iwasaki, Shintaro Doi, Masao https://orcid.org/0000-0001-6264-9217 (unconfirmed) |
著者名の別形: | 三宅, 崇仁 井ノ上, 雄一 邵, 欣彦 瀬田, 孟仁 青木, 祐人 グエンファム, カンティエン 七野, 悠一 佐々木, 純子 佐々木, 雄彦 伊川, 正人 山口, 賀章 岡村, 均 岩崎, 信太郎 土居, 雅夫 |
キーワード: | circadian clock body temperature entrainment translation uORF Per2 PI3K |
発行日: | 28-Mar-2023 |
出版者: | Elsevier BV |
誌名: | Cell Reports |
巻: | 42 |
号: | 3 |
論文番号: | 112157 |
抄録: | Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C–38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5′ UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology. |
記述: | 全身の体内リズムを調和させるRNA配列の発見 --体温の日内変化に合わせてしなやかに調和させる--. 京都大学プレスリリース. 2023-03-07. |
著作権等: | © 2023 The Author(s). This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license. |
URI: | http://hdl.handle.net/2433/281515 |
DOI(出版社版): | 10.1016/j.celrep.2023.112157 |
PubMed ID: | 36882059 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2023-03-07-0 |
出現コレクション: | 学術雑誌掲載論文等 |
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