アポトーシス中のミトコンドリアからのPNPT1放出は,ポリ (A) RNAの分解を誘発する
Xing Liu1, Rui Fu1, Youdong Pan2
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|May 22, 2018
まとめ
PNPT1のミトコンドリアの放出は,アポトーシス中に広範囲に広がるRNAの崩壊を誘発し,細胞死を促進する. このプロセスは特定のRNAを標的とし プログラムされた細胞死における新しいメカニズムを明らかにします
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- 広範囲に広がるmRNAの衰退はアポトーシスの重要な要素ですが まだ十分に研究されていません
- アポプトティックRNA崩壊はミトコンドリア外膜浸透 (MOMP),TUTases,およびDIS3L2に依存する.
- 標的となる特定のRNAとアポプトシス崩壊の開始因子は,ほとんど不明である.
研究 の 目的:
- アポトーシス中に衰退するRNAを特定する.
- アポトーシスにおける広範囲のRNA崩壊を誘発する分子イベントを明らかにする.
- ミトコンドリア因子のアポプトティックRNA崩壊における役割を理解する.
主な方法:
- ミトコンドリアタンパク質のノックダウンと過剰発現を用いてアポトーシス中のRNA分解を調査した.
- PNPT1の基板特異性を決定するために,RNaseアッセイと構造分析を使用した.
- RNA 3'端構造の腐敗感受性への影響を調べた.
主要な成果:
- ミトコンドリアの外核酵素であるPNPT1を,アポトーシス中の広範なmRNAおよび非コーディングRNAの崩壊のトリガーとして特定した.
- MOMP中のPNPT1の放出は,保護構造が欠けているRNAの3'端の分解を誘発する.
- RNA 3' 幹のループ構造を破壊すると腐敗が増加し,それらを追加すると抵抗性が生じます.
結論:
- MOMP中のミトコンドリアからのPNPT1放出は,アポプトティックRNA崩壊の開始イベントです.
- アポプトティックRNAの分解は,mRNAやポリ・ア・ノンコーディングRNAなどの,3'端がアクセス可能なRNAを優先的に標的とする.
- RNAの構造要素は,PNPT1媒介の衰退に対する感受性を決定し,アポトーシスの規制メカニズムを強調する.
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