lincRNAsは,多能性と分化を制御する回路で作用する
Mitchell Guttman1, Julie Donaghey, Bryce W Carey
1Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. mguttman@mit.edu
Nature
|August 30, 2011
まとめ
大型のインタージェニック・ノンコーディングRNA (lincRNAs) は,胚性幹細胞の状態を維持する上で重要な役割を果たします. 私たちの研究では,リンカRNAが遺伝子発現と細胞分化プログラムに大きく影響していることが明らかになりました.
科学分野:
- ゲノミクスゲノミクスとは
- 発達生物学 発達生物学とは
- RNA 生物学 RNA 生物学
背景:
- 何千もの大きな遺伝子間非コーディングRNA (lincRNAs) が特定されていますが,その機能はほとんど不明です.
- lincRNAsの生物学的な役割を理解することは,細胞の調節を解読するために不可欠です.
研究 の 目的:
- マウスの胚性幹細胞 (ES細胞) のリンカRNAを機能的に特徴付ける.
- lincRNAの機能喪失が遺伝子発現とES細胞の状態に与える影響を調査する.
主な方法:
- マウスのES細胞で発現するlincRNAsの大部分について,機能喪失に関する研究が行われました.
- lincRNAのノックダウン後に遺伝子発現パターンを分析した.
主要な成果:
- lincRNAsのノックダウンは,既知のES細胞の調節体と比較して,遺伝子発現を著しく変えました.
- lincRNAsは,主にトランスでの遺伝子発現に影響することが判明しました.
- 数十の lincRNAs は,ノックダウン後,多能性からの脱出を誘導したり,系統のコミットメントプログラムを活性化したりしました.
- lincRNA遺伝子は重要な転写因子によって調節され,それらの転写は染色体調節タンパク質と相互作用する.
結論:
- lincRNAsは,ES細胞のアイデンティティを制御する分子回路の不可欠な構成要素です.
- これらの非コーディングRNAは,多能性を維持し,細胞の運命を決定する上で重要な役割を果たします.
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