Tet2は,mRNAの酸化によって病原体感染による骨髄形成を促進する
Qicong Shen1, Qian Zhang1,2, Yang Shi3
1National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Nature
|January 25, 2018
まとめ
Tet2はmRNAの5メチルサイトシン (5- mC) を減らし,Adar1経由でSocs3発現に影響を与え,感染誘発性骨髄形成を促進する. これは,哺乳類の免疫における Tet2 の新たな表表表記学的役割を明らかにしている.
科学分野:
- エピトランスクリプトミクス
- 免疫学
- 分子生物学
背景:
- RNAの改変を含むエピトランスクリプトームは,転写後の遺伝子発現を調節する.
- 哺乳類のmRNAにおける5-メチルサイトシン (5-mC) とその機能は,大部分は特徴づけられていない.
- 十""の転位 (Tet) タンパク質,特にTet2は,DNA脱メチル化で知られており,炎症および骨髄性悪性腫瘍に役割があります.
研究 の 目的:
- 哺乳類のmRNAにおける5メチルサイトシン (5-mC) の役割とメカニズムを解明する.
- 感染誘発性骨髄形成における Tet2 の機能を調査する.
- Tet2によってSocs3発現の表記体調節を特定する.
主な方法:
- mRNA改変に関連した Tet2の酵素活性の分析
- Tet2,Adar1,およびSocs3 mRNAの相互作用を調査する.
- 感染モデル (セプシス,寄生虫) でのミエロポエーシスとmRNAメチル化パターンの影響の研究.
主要な成果:
- Tet2は,Socs3 mRNAのレベルを低下させることで,感染誘発の骨髄形成とマスト細胞の膨張を促進します.
- Tet2は,RNA編集とは無関係に,Adar1によるSocs3 mRNAの不安定化によってSocs3の発現を抑制する.
- Tet2はmRNAにおける5 - mCの酸化を媒介し,Tet2の欠乏はmRNAにおける5 - mCの増加につながり,Adar1結合に影響する.
結論:
- Tet2は,mRNAの5 - mCsを減少させることで,感染中に哺乳類の骨髄形成を促進する上で重要な表表記学的役割を果たします.
- Tet2媒介によるmRNAメチレーションは,二重鎖RNA形成とAdar1結合に影響を与え,新しい生理学的機能を明らかにする.
- この研究は,Tet2,表写体学,および先天性免疫を含む新しい調節経路を発見しました.
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