RNAの干渉とX不活性化経路の交差点.
Yuya Ogawa1, Bryan K Sun, Jeannie T Lee
1Department of Molecular Biology, Massachusetts General Hospital and Howard Hughes Medical Institute, Boston, MA 02114, USA.
まとめ
哺乳類のX染色体不活性化 (XCI) は,XistとTix RNAsを含む. 彼らの相互作用は,RNA干渉 (RNAi) を通して小さなRNAs (sRNAs) を生成し,不活性X染色体を静止するのに不可欠です.
科学分野:
- 遺伝学 遺伝学とは
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
背景:
- 哺乳類の用量補償は,雌のX染色体不活性化 (XCI) に依存しています.
- Xist遺伝子はX染色体サイレンスを開始し,TsixRNAは抗体として作用する.
- XistとTixのRNAの互補性は,RNA干渉 (RNAi) の役割を示唆しています.
研究 の 目的:
- X染色体不活性化におけるRNA干渉の役割を調査する.
- XCI中にXistとTixRNAが相互作用するメカニズムを解明する.
- Xist/Tsix複合体から派生した小さなRNAの機能を決定する.
主な方法:
- XistとTixのRNAデュプレックス形成の分析 in vivo.
- 小型RNA (sRNA) へのXist/Tsix複合体のDicer依存処理の調査.
- Xist RNAレベル,ヒストンのメチル化,XCIに対するDicer消去効果の評価.
- Tsixの切断による救助実験の評価.
主要な成果:
- ミュアンのXistとTsixRNAは,体内で複合体を形成する.
- これらの二重複体は,XCI.の間,Dicer依存的な方法でsRNAに処理されます.
- Dicerの消去は,sRNAの産生を阻害し,Xistを消去し,Xist RNAの蓄積とH3K27のトリメチル化を不活性なXで阻害する.
- Tsixの切断は,これらの欠陥を部分的に救済します.
結論:
- RNA干渉 (RNAi) とX染色体不活性化 (XCI) は相互に関連したプロセスである.
- Xist/Tsix複合体のディカー媒介処理は,Xist発現を調節する.
- このメカニズムは,活性X染色体におけるXistのダウンレギュレーションと,非活性X染色体におけるサイレンスに寄与する.
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