mTORC1と筋肉再生は,LINC00961でコードされたSPARポリペプチドによって制御されます
Akinobu Matsumoto1, Alessandra Pasut1, Masaki Matsumoto2
1Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Nature
|December 27, 2016
まとめ
研究者らは,長い非コーディングRNA LINC00961によって暗号化された隠されたポリペプチド,SPARを発見しました. SPARはアミノ酸によるmTORC1の活性化を調節し,損傷後の筋肉再生に不可欠です.
科学分野:
- 分子生物学
- 遺伝学
- 細胞生物学
背景:
- 長い非コーディングRNA (lncRNAs) は,非コーディングの役割を超えた機能のためにますます認識されています.
- lncRNAの中には,機能的なポリペプチドに変換できる小さなオープン・リーディングフレーム (ORF) がある.
- lncRNAでコードされたこれらのポリペプチドの生物学的な意義は,ほとんど未知のままです.
研究 の 目的:
- lncRNA LINC00961でコードされた新しいポリペプチドを識別し,機能的に特徴づける.
- 細胞信号伝達経路と組織再生におけるこのポリペプチドの役割を明らかにする.
主な方法:
- LINC00961から新しいポリペプチド (SPAR) の識別と特徴付け.
- SPARの局所化と相互作用 (例えばv-ATPase) を決定する生化学的測定法.
- CRISPR/Cas9遺伝子編集により,SPAR特有のノックアウトマウスモデルが作成されます.
- 急性損傷後の筋肉再生を評価する in vivo 研究
主要な成果:
- LINC00961から保存されたポリペプチド,SPARが特定され,後期エンドソーム/ライソームに局所されました.
- SPARはv- ATPaseと相互作用し,アミノ酸刺激によるmTORC1の活性化を否定的に調節する.
- SPARのノックアウトマウスは,mTORC1の活性化と損傷後の筋肉再生の改善を示した.
- LncRNAのLINC00961発現は,骨格筋の損傷後のダウンレギュレーションです.
結論:
- 新種のlncRNAでコードされたポリペプチドであるSPARは,アミノ酸の可用性に応じてmTORC1の活性化を微調整するメカニズムを提供します.
- この経路は 損傷後の効率的な筋肉再生に不可欠です
- lncRNAは小さなポリペプチドをコードし,組織特有の必要性のために基本的な生物学的プロセスを調節します.
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