Miliのエンドヌクレアース活動は,LINE1要素を静止させるpiRNA増幅を促します
Serena De Fazio1, Nenad Bartonicek, Monica Di Giacomo
1European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy.
Nature
|October 25, 2011
まとめ
ミリのようなピウィタンパク質は,LINE1トランポゾンを静止させるため,piRNA (Piwi相互作用RNA) を増幅するために不可欠です. ミリを混乱させる.
科学分野:
- 生殖生物学 生殖生物学
- 分子遺伝学 分子遺伝学
- エピジェネティクス エピジェネティクス
背景:
- Piwiタンパク質とpiRNAは,トランポゾンサイレンシングに不可欠であり,特に生殖細胞の発達期に不可欠です.
- ミリとMiwi2は,LINE1と内側A粒子 (IAP) トランポゾンの表遺伝的静止に関与するネズミのPiwiタンパク質です.
- piRNAの生体生成とトランポゾン制御におけるPiwiタンパク質のエンドヌクレアース活性が果たす正確な役割は不明である.
研究 の 目的:
- piRNA生殖とトランポゾンサイレンシングにおけるPiwi触媒によるエンドヌクレアース活動の機能的重要性を調査する.
- これらのプロセスにおけるMiliとMiwi2の特定の役割を解明するために,触媒的に不活性な変異体を分析する.
- LINE1とIAPのトランポゾン静止と男性の生育能力に対するPiwiエンドヌクレアースの活性への貢献を決定する.
主な方法:
- ミリとMiwi2の触媒DDHトライアドの点変異を持つマウスの生成,ミリ (((DAH)) とミウィ2 (((DAH)) アレルを作成します.
- 変異したマウスの性腺細胞におけるpiRNA集団とトランポゾンサイレンシングの分析.
- ミリ ((DAH) とミウィ2 ((DAH) ホモジゴスマウスにおける生育能力と精子生成の評価.
主要な成果:
- Mili (((DAH) 変異により,piRNAの増幅が妨げられ,Miwi2複合体内のpiRNAが減少し,LINE1サイレンシングが損なわれた.
- ミリ媒介のpiRNA増幅はLINE1サイレンシングには不可欠ですが,IAPサイレンシングには必要ありません.
- ホモジゴスミウイ2 ((DAH) マウスは,正常なトランポゾン静止と二次的なpiRNA生体生成で,肥沃であり,増幅におけるミリの主要な役割を示している.
- 欠陥のpiRNA経路がミリ・ダヒマウスの精子生成機能不全と不妊症を引き起こした.
結論:
- Intra-Mili二次的なpiRNAバイオゲネシスは,LINE1サイレンシングに不可欠なpiRNA増幅を駆動します.
- Miliのエンドヌクレアース活動は,piRNAの増幅とLINE1の静止に不可欠であり,男性の生育能力に影響を与えます.
- Miwi2のエンドヌクレアース活動は,男性生殖系におけるpiRNA増幅またはLINE1静止には不可欠ではありません.
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