DDX5と関連するlncRNA RmrpはTH17細胞エフェクタ機能を調節する
Wendy Huang1, Benjamin Thomas2, Ryan A Flynn3
1The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
Nature
|December 18, 2015
まとめ
DEAD- box protein 5 (DDX5) は,RORγtと提携し,Tヘルパー17 (TH17) 細胞の分化を調節する. この相互作用は,Rmrpの長いノンコーディングRNAに依存し,TH17媒介の炎症には極めて重要です.
科学分野:
- 免疫学
- 分子生物学
- 遺伝学
背景:
- Tヘルパー17 (TH17) 細胞は粘膜免疫に不可欠ですが,慢性炎症疾患に関与しています.
- TH17細胞の分化は核受容体RORγtによって調節される.
研究 の 目的:
- TH17細胞機能に関与するRORγtの新しいパートナーを特定する.
- TH17媒介病理におけるRNAヘリコースと長いノンコーディングRNAの役割を解明する.
主な方法:
- タンパク質の相互作用を特定するための共免疫流出.
- lncRNAの関与を評価するRNA結合測定法
- 標的遺伝子の転写を定量化するための遺伝子発現分析
- 標的となる遺伝子変異を持つマウスモデル
主要な成果:
- DEAD- box protein 5 (DDX5) は,RORγtと相互作用するパートナーとして特定されました.
- RORγtとDDX5の相互作用と転写的同活性化は,そのRNAヘリケーゼ活性とRmrp lncRNAに依存する.
- Rmrpの軟骨-毛の低増殖変異を模倣したマウスモデルでは,DDX5- RORγtの相互作用が低下し,TH17遺伝子転写が低下した.
結論:
- DDX5とRmrpは,TH17細胞の分化を調節するRORγt転写複合体の重要な構成要素である.
- この発見は,組織特異的な遺伝子調節にRNAヘリコースとlncRNAが関与する新しいメカニズムを明らかにしています.
- この研究は,TH17依存性炎症疾患に対する潜在的な治療目標を提供します.
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