N6-メチラデノシンは,処理のためのプライマリマイクロRNAをマークします
Claudio R Alarcón1, Hyeseung Lee1, Hani Goodarzi1
1Laboratory of Systems Cancer Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Nature
|March 25, 2015
まとめ
メチルトランスフェラーゼ類似3 (METTL3) は,プリミRNAにm(6) Aマークを追加し,DGCR8の認識とマイクロRNAの処理を可能にします. この改変は,miRNAの生体生成とグローバルなmiRNAレベルにとって不可欠である.
科学分野:
- 分子生物学は分子生物学である.
- RNA 生物学 RNA 生物学
- エピジェネティクス エピジェネティクス
背景:
- マイクロRNA (miRNA) のバイオゲネシスは,マイクロプロセッサ複合体 (DGCR8/DROSHA) によるプライマリ・ミRNA (プリ-ミRNA) の処理によって開始されます.
- 他のRNA構造に対するプリミRNAのDGCR8認識の正確なメカニズムは不明である.
研究 の 目的:
- DGCR8がプリミRNAを認識し結合するメカニズムを解明する.
- miRNAバイオゲネシスの初期段階を調節する要因を特定する.
主な方法:
- METTL3の枯渇と機能の獲得を含む細胞実験.
- 実験室内加工反応を含む生化学分析.
- プリミRNAと成熟ミRNAのレベルを分析する.
主要な成果:
- METTL3は,N(6) -メチラデノシン (m(6) A部位でプリミRNAをメチラ化し,DGCR8結合のためにそれらをマークします.
- METTL3の枯渇は,DGCR8-プリ-ミRNAの相互作用を減少させ,成熟したミRNAの減少とプリ-ミRNAのレベルの増加につながります.
- 実験室内研究では,primi-miRNA処理に十分なm(6) Aが確認され,METTL3は,全世界的にmiRNAの成熟を向上させる.
結論:
- METTL3によって媒介されるm(6)A変異は,DGCR8によるプリミRNAの認識と処理を促進する重要なポストトランスクリプションの調節体である.
- この発見は,miRNAバイオゲネシスの開始を制御する新しいメカニズムを明らかにしています.
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