RNAメチル化に依存するRNA処理は,日中時計の速度を制御する
Jean-Michel Fustin1, Masao Doi, Yoshiaki Yamaguchi
1Graduate School of Pharmaceutical Sciences, Department of System Biology, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Cell
|November 12, 2013
まとめ
m(6) A-RNAメチル化を含むトランスメチル化反応の抑制により,昼間の周期が延長されます. これはRNA処理と時計遺伝子のリズム表現に影響する.
科学分野:
- クロノバイオロジー クロノバイオロジー
- 分子生物学は分子生物学である.
- RNA 生物学 RNA 生物学
背景:
- ユカリオット生物学的時計は,転写-翻訳フィードバックループに依存しています.
- mRNAの処理は,単なる転写ではなく,肝臓の転写体の約10%がリズミカルな発現を示す,重要な昼夜構成要素です.
研究 の 目的:
- サーカディアンリズムを調節するトランスメチル化反応の役割を調査する.
- 関連する特定のRNA変異と,時計遺伝子発現とRNA処理に与える影響を特定する.
主な方法:
- トランスメチル化反応の抑制と,その後の昼間周期測定.
- RNA処理機械における転写変化を分析するためのRNA配列解析.
- メチラーゼMettl3.6Aを静止する
- 時計遺伝子Per2とArntlの昼間核細胞プラズマ分布の分析.
主要な成果:
- トランスメチル化反応の抑制により,昼夜周期が著しく延長されます.
- RNAの配列解析により,RNA処理機構における広範囲にわたる転写変化が明らかになり,これはm(6) A-RNAメチル化に関連している.
- Mettl3サイレンシングによるm(6) Aメチル化の特定の阻害は,周期延長とRNA処理の遅延を引き起こしました.
- m(6) メチル化阻害により,時計遺伝子のプレ-mRNAとサイトプラズミックmRNAのリズムが分離した.
結論:
- トランスメチル化,特にm(6) A-RNAメチル化は,真核生物の昼夜時計の重要な調節因子である.
- m(6) 時計遺伝子トランスクリプトの改変がRNA処理とリズム的な遺伝子発現に影響を与える.
- m(6) Aメチル化の障害は,mRNA処理の調整と生物学的時計のリズム出力に影響する.
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