MIR-NATはMAPT翻訳を抑制し,神経変性におけるプロテオスタシスを支援する
Roberto Simone1,2, Faiza Javad3,4, Warren Emmett5,6,7
1Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, UK. r.simone@ucl.ac.uk.
Nature
|May 20, 2021
まとめ
自然な反意味トランスクリプト (NAT) は遺伝子発現を制御する. MAPT-AS1は脳を豊かにするNATで,タウ変換を抑制し,タウ病や神経変性疾患に影響を与えます.
科学分野:
- 神経科学
- 分子生物学
- 遺伝学
背景:
- 遺伝子発現を複数のレベルで 制御しています
- MAPTはタウをコードします これは前頭葉性認知症やパーキンソン病のような 神経退行性疾患に 関わるタンパク質です
- タウの調節不良は,タンパク質の含有によって特徴づけられるタウ病と関連しています.
研究 の 目的:
- MAPT-AS1の働きを 調べるためだ
- タウ変換の調節におけるMAPT-AS1の役割と,タウ病に対するその関連性を決定する.
- 神経変性におけるMIR-NATのより広範な役割を調査する.
主な方法:
- MAPT-AS1の特徴,保存された性質と埋め込まれたMIR要素を含む.
- MAPT-AS1がタウ変換とニューロンのタウレベルに及ぼす影響を評価する試験.
- 神経変性および本質的に乱れたタンパク質 (IDP) に関連する遺伝子におけるMIR-NATの分析.
主要な成果:
- MAPT- AS1は,MAPT mRNAへのリボソーム結合を妨害することによって,タウ変換を抑制するMIR要素を含んでいます.
- MAPT-AS1の発現は,神経のタウレベルと人間の脳のタウ病理と逆相関しています.
- PLCG1に対するMIR- NAT媒介トランスレーション制御が確認され,神経変性およびIDPに関連した遺伝子で強化された追加のMIR- NATが特定されました.
結論:
- MAPT-AS1は,タウ伝達を調節することによって,タウ病に重要な役割を果たします.
- MIR-NATは,IDPの翻訳を制御するための潜在的に広範なメカニズムを表しています.
- これらの発見は,MIR-NATがプロテオスタシスと神経変性における重要性を強調しています.
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