このアイテムのアクセス数: 46

このアイテムのファイル:
ファイル 記述 サイズフォーマット 
pnas.1721371115.pdf1.27 MBAdobe PDF見る/開く
タイトル: Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock
著者: Fustin, Jean-Michel  kyouindb  KAKEN_id
Kojima, Rika
Itoh, Kakeru
Chang, Hsin-Yi
Shiqi, Ye
Zhuang, Bowen
Oji, Asami
Gibo, Shingo
Narasimamurthy, Rajesh
Virshup, David
Kurosawa, Gen
Doi, Masao  kyouindb  KAKEN_id
Manabe, Ichiro
Ishihama, Yasushi  kyouindb  KAKEN_id
Ikawa, Masahito
Okamura, Hitoshi
著者名の別形: 小島, 莉果
伊藤, 翔
張, 心儀
大字, 亜沙美
儀保, 伸吾
黒澤, 元
土居, 雅夫
真鍋, 一郎
石濱, 泰
伊川, 正人
岡村, 均
キーワード: casein kinase
circadian
methylation
splicing
m6A
発行日: 5-Jun-2018
出版者: National Academy of Sciences
誌名: Proceedings of the National Academy of Sciences
巻: 115
号: 23
開始ページ: 5980
終了ページ: 5985
抄録: The N6-methylation of internal adenosines (m6A) in mRNA has been quantified and localized throughout the transcriptome. However, the physiological significance of m6A in most highly methylated mRNAs is unknown. It was demonstrated previously that the circadian clock, based on transcription-translation negative feedback loops, is sensitive to the general inhibition of m6A. Here, we show that the Casein Kinase 1 Delta mRNA (Ck1δ), coding for a critical kinase in the control of circadian rhythms, cellular growth, and survival, is negatively regulated by m6A. Inhibition of Ck1δ mRNA methylation leads to increased translation of two alternatively spliced CK1δ isoforms, CK1δ1 and CK1δ2, uncharacterized until now. The expression ratio between these isoforms is tissue-specific, CK1δ1 and CK1δ2 have different kinase activities, and they cooperate in the phosphorylation of the circadian clock protein PER2. While CK1δ1 accelerates the circadian clock by promoting the decay of PER2 proteins, CK1δ2 slows it down by stabilizing PER2 via increased phosphorylation at a key residue on PER2 protein. These observations challenge the previously established model of PER2 phosphorylation and, given the multiple functions and targets of CK1δ, the existence of two isoforms calls for a re-evaluation of past research when CK1δ1 and CK1δ2 were simply CK1δ.
記述: 体内リズムの24時間周期を決めるタンパク質を発見 --家族性睡眠相前進症候群(FASPS)の分子機構の解明--. 京都大学プレスリリース. 2018-05-23.
著作権等: © 2018 the Author(s). This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
URI: http://hdl.handle.net/2433/231231
DOI(出版社版): 10.1073/pnas.1721371115
PubMed ID: 29784786
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/180522_3.html
出現コレクション:学術雑誌掲載論文等

アイテムの詳細レコードを表示する

Export to RefWorks


出力フォーマット 


このリポジトリに保管されているアイテムはすべて著作権により保護されています。