SMADタンパク質はDROSHA媒介によるマイクロRNAの成熟を制御する
Brandi N Davis1, Aaron C Hilyard, Giorgio Lagna
1Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Nature
|June 13, 2008
まとめ
変形成長因子β (TGF-β) と骨形態遺伝タンパク質 (BMP) のシグナル伝達により,マイクロRNA-21 (miR-21) レベルが急速に上昇します. これは,収縮性遺伝子の負の調節体であるPDCD4をダウンレギュレーションすることによって,血管の滑らかな筋肉細胞の収縮を高めます.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- マイクロRNA (miRNA) は遺伝子発現を調節するが,その生体生成の制御は十分に理解されていない.
- 変換成長因子β (TGF-β) と骨形態遺伝タンパク質 (BMP) のシグナル伝達経路は,血管の発達とホメオスタシスにとって極めて重要です.
- 調節不良のmiRNA発現は,がんや心血管疾患などの疾患に関連しています.
研究 の 目的:
- TGF-βおよびBMP誘発性血管滑らかな筋肉細胞のフェノタイプにおけるマイクロRNAの役割を調査する.
- TGF-βとBMPのシグナル伝達がmiRNAのバイオゲネシスを調節するメカニズムを解明する.
主な方法:
- 定量的リアルタイムPCRでmiRNAと遺伝子発現を測定する.
- タンパク質のレベルを評価するためのウェスタン・ブロッティング.
- タンパク質とRNAの相互作用を研究するための免疫プレシピテーションアッセイ.
主要な成果:
- TGF-βとBMPのシグナリングは,miR-21経由で血管の滑らかな筋肉細胞の収縮を誘導する.
- miR-21は,滑らかな筋肉の収縮性遺伝子の抑制体であるPDCD4を直接ダウン調節する.
- TGF-βとBMPのシグナル伝達は,ドロシャ複合体によるプリミR-21の転写後の処理を通じて成熟したmiR-21の産生を促進する.
- SMADタンパク質とp68/DDX5がprimiR-21に誘導され,SMAD4から独立して処理が容易になります.
結論:
- TGF-βとBMPのシグナル伝達は,miR-21を通して,血管の滑らかな筋肉細胞のフェノタイプを調節する.
- リンガン特異のSMADタンパク質は,トランスクリプション後のレベルでmiRNAの生殖を制御する.
- このメカニズムは,TGF-βおよびBMPシグナル伝達におけるSMAD4独立の規制経路を強調しています.
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