DDX5及其相关的 lncRNA Rmrp 调节TH17细胞效应器功能
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
概括
一种RNA螺旋酶的DEAD盒蛋白5 (DDX5) 与RORγt合作调节T辅助细胞17 (TH17) 的分化. 这种依赖Rmrp长非编码RNA的相互作用对于TH17介导的炎症至关重要.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 辅助T细胞17 (TH17) 对于粘膜免疫至关重要,但涉及慢性炎症疾病.
- TH17细胞分化由核受体RORγt进行调节.
研究的目的:
- 确定参与TH17细胞功能的RORγt的新合作伙伴.
- 阐明RNA螺旋酶和长非编码RNA在TH17介导病理中的作用.
主要方法:
- 共同免疫沉以确定蛋白质相互作用.
- 用于评估 lncRNA 的参与的RNA 结合测试.
- 基因表达分析以量化目标基因转录.
- 具有向基因突变的小鼠模型.
主要成果:
- 被确定为与RORγt相互作用的DEAD盒蛋白5 (DDX5).
- DDX5与RORγt的相互作用和转录协活性取决于其RNA酶活性和Rmrp lncRNA.
- 模仿Rmrp软骨-毛发低成形突变的小鼠模型显示DDX5- RORγt相互作用受损并减少TH17基因转录.
结论:
- DDX5和Rmrp是调节TH17细胞分化的RORγt转录复合物的重要组成部分.
- 这些发现揭示了一种涉及RNA螺旋酶和lncRNAs在组织特异性基因调节中的新机制.
- 这项研究为TH17依赖性炎症疾病提供了潜在的治疗点.
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