プロモーターに結合したMETTL3は,m6A依存の翻訳制御によって骨髄性白血病を維持する
Isaia Barbieri1, Konstantinos Tzelepis2, Luca Pandolfini1
1The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Nature
|November 30, 2017
まとめ
METTL3は急性骨髄性白血病 (AML) の細胞成長に不可欠です. この酵素はRNAの改変によって遺伝子発現を調節し,AMLの治療対象となる可能性がある.
科学分野:
- 分子生物学
- エピジェネティクス
- 癌 研究
背景:
- N6-メチラデノシン (m6A) は,一般的なRNA変異である.
- がんにおけるm6Aメチルトランスフェラーゼ複合体 (METTL3- METTL14) の役割は不明である.
研究 の 目的:
- 急性骨髄性白血病 (AML) のMETTL3の特異的な機能を明らかにする.
- METTL3をAMLの潜在的な治療標的として特定する.
主な方法:
- AML細胞の成長に不可欠な遺伝子を特定する遺伝子スクリーニング
- 遺伝子調節を分析するためのクロマチン免疫降水とRNAシーケンシング.
- 細胞サイクル,分化,腫瘍形成の評価 in vivo
主要な成果:
- METTL3はAML細胞増殖と白血病状態の維持に不可欠です.
- METTL3はMETTL14とは独立して活性遺伝子プロモーターに局所化し,CEBPZによって採用されます.
- METTL3は,リボソームの停滞を緩和し,AMLにとって重要な遺伝子を調節することにより,mRNAの翻訳を強化します.
結論:
- METTL3は,AMLに不可欠なクロマチンベースの経路を調節する.
- METTL3は急性骨髄性白血病の有望な治療標的である.
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