ミトコンドリアの二重鎖RNAは,ヒトにおける抗ウイルス信号を誘発する
Ashish Dhir1, Somdutta Dhir2, Lukasz S Borowski3,4
1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. ashish.dhir@path.ox.ac.uk.
Nature
|July 27, 2018
まとめ
研究者らは 細胞内の不安定なミトコンドリアの二重鎖RNAを発見しました 主要な酵素SUV3とポリヌクレオチドリン酸化酵素 (PNPase) は,そのレベルを制限し,免疫活性化を防ぐ.
科学分野:
- 細胞生物学
- 免疫学
- 分子生物学
背景:
- エンドシンビオティックな細菌から生まれたミトコンドリアは,双方向転写の対象となる円形のゲノムを持っています.
- 哺乳類におけるこのプロセスは,重複するトランスクリプトを生成し,潜在的に二重鎖RNA (dsRNA) を形成する.
- ミトコンドリアのdsRNAのin vivo存在と機能は,大部分は特徴づけられていなかった.
研究 の 目的:
- 生体内におけるネイティブミトコンドリアの二重鎖RNAを特徴づける.
- ミトコンドリアの dsRNA レベルを調節する細胞因子を特定する.
- ミトコンドリアのdsRNAと先天的な免疫活性化との関係を調査する.
主な方法:
- ミトコンドリア dsRNAを検出するための単細胞分析
- マウスにおけるミトコンドリアRNAヘリゼSUV3とポリヌクレオチドリン酸化酵素 (PNPase) の遺伝子操作.
- MDA5とI型インターフェロン反応を含む免疫信号伝達経路の分析
- PNPT1変異を有する患者の臨床データ分析
主要な成果:
- 単細胞レベルで高度に不安定なネイティブミトコンドリア dsRNA 種が検出されました.
- SUV3またはPNPaseの喪失は,ミトコンドリア dsRNAの重要な蓄積につながった.
- ミトコンドリアのdsRNAは細胞質に逃れ,MDA5を活性化し,タイプIインターフェロン反応を誘発した.
- PNPT1変異の患者はミトコンドリア dsRNAの蓄積と免疫活性化マーカーを示した.
結論:
- SUV3とPNPは,ミトコンドリアのdsRNAレベルを制限し,その細胞質の放出を防止するために不可欠です.
- PNPaseはミトコンドリア内のミトコンドリア dsRNAを管理する二重の役割を果たします.
- ミトコンドリアの dsRNA の蓄積は,ウイルスの感染を模倣して,不適切な形で先天的な免疫防御を活性化させる可能性があります.
- ミトコンドリア dsRNA 処理の調節不良はヒトの免疫障害と関連している.
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