早期の転写終結の遺伝的抑制は,分裂酵母分裂およびポリアデニレーション機構の重要なサブユニットの変異を特定する
Aleksei Innokentev1, Ana M Sanchez1, Lauren Bednor2
1Memorial Sloan Kettering Cancer Center.
まとめ
分裂酵母酸ホメオスタシスは lncRNAの調節を伴う. Msi2のような重要なCPFサブユニットの新しい突然変異は,変化したイノシトールパイロフォスファートの毒性を抑制し,新しい調節経路を明らかにします.
科学分野:
- 分子生物学
- 遺伝子規制
- RNA 処理
背景:
- 分裂酵母のリン酸獲得 (PHO) レギュロンは,リン酸補充条件下でlncRNA媒介の転写干渉によって抑制されます.
- イノシトール-1-パイロフォスファートは,PHO lncRNA 3'-処理/終了を促進することによって,リン酸ホメオスタシスを調節する.
- イノシトールパイロフォスファートに影響する変異は,PHO遺伝子の減圧と成長障害を引き起こし,不必要の割れ分とポリアデニレーション因子 (CPF) の前回の抑制が観察されました.
研究 の 目的:
- 核分裂酵母におけるパイロフォスファターゼ誘発の新種の遺伝抑制剤を特定する.
- PHO lncRNAの終結とリン酸ホメオスタシスの調節における重要なCPFサブユニットの役割を解明する.
- イノシトール・パイロフォスファートシグナル伝達とCPF複合体の遺伝子発現制御における相互作用を理解する.
主な方法:
- asp1-STFパイロフォスファタゼ変異体の成長欠陥を抑制する自発的な変異のスクリーニング
- 重要なCPFサブユニット (Ysh1,Pta1,Pfs2,Cft1,Msi2,Iss1) とPla1の変異の特徴づけ
- CPFサブユニット,終結因子,および調節性キナーゼの間の変異シナジーを分析するための遺伝子クロス.
主要な成果:
- 5つの重要なCPFサブユニット (Ysh1,Pta1,Pfs2,Cft1,Msi2) と Iss1で新しい低形変異が確認されました.
- Pla1の活性部位の変異は asp1- STFの毒性を抑制した.
- 遺伝子分析により,合成による致死性を示すイノシトール-1-パイロフォスファートと並行して,Msi2が3'-処理/終結において中心的に作用する相互作用の階層が明らかになった.
結論:
- 必須のCPFサブユニットは,PHO lncRNAの終結とリン酸ホメオスタシスにおいて重要な役割を果たします.
- Msi2は,3'-処理/終末装置の重要な構成要素であり,独立して機能するが,イノシトール-1-パイロフォスファートと並行して機能する.
- これらの経路を理解することで 遺伝子の調節と 栄養素の利用可能性に対する 細胞の反応の洞察が得られます
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