変異したmRNAの分解によって引き起こされる遺伝的補償
Mohamed A El-Brolosy1, Zacharias Kontarakis1, Andrea Rossi1,2
1Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Nature
|April 5, 2019
まとめ
生物は,変異のmRNAの分解を必要とするプロセスである転写適応によって変異に適応することができる. この適応は類似した遺伝子を高調化し 病気の変異の理解と補償戦略に影響を与えます
科学分野:
- 遺伝学
- 分子生物学
- 発達生物学
背景:
- 遺伝的強さは,しばしばタンパク質のフィードバックループを通じて,変異にもかかわらず,生物の健康状態を維持します.
- 関連する遺伝子がタンパク質フィードバックから独立して上位調節されるトランスクリプション適応は,提案されているが,理解されていないメカニズムである.
- 転写による適応の流行と分子基盤は,ほとんど不明である.
研究 の 目的:
- 変異に反応する転写適応の分子メカニズムと流行を調査する.
- 転写適応における変異mRNAの分解の役割を決定する.
- トランスクリプション適応の配列依存性について調べる
主な方法:
- 斑馬魚とマウスの転写適応モデルの分析.
- 変異したmRNAの衰退とないアレルの間のフェノタイプの比較.
- 変異したmRNAの崩壊を示すアレルのトランスクリプトーム解析.
主要な成果:
- 変異したmRNAの分解は転写適応に不可欠であり,それがないアレルは適応しない.
- 変異したmRNAの崩壊を持つアレルは,変異していないアレルと比較してより重度のフェノタイプを示します.
- トランスクリプトーム解析は,変異した遺伝子のmRNAに配列の類似性を持つ遺伝子のアップレギュレーションを明らかにし,配列に依存するメカニズムを示しています.
結論:
- 変異したmRNAの分解は,転写適応の重要な要件である.
- トランスクリプションによる適応は 変異を補うことができる 配列に依存するプロセスです
- これらのメカニズムの理解は,補償が低下した病気を引き起こす変異性アレルの設計に情報を与えることができます.
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