在细菌感染期间,DDX5通过调节TLR2/4转录的m6A水平来抑制炎症
Jian Xu1, Li-Yuan Liu1, Fei-Jie Zhi1
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
EMBO reports
|January 5, 2024
概括
DDX5蛋白通过控制托尔类受体 (TLR) 2和4的表达来调节细菌感染炎症. 它在感染期间的降解促进炎症,突出DDX5作为关键的炎症调节剂.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 在RNA代谢过程中.
背景情况:
- DExD/H盒酶调节RNA代谢和抗病毒免疫力.
- 这些螺旋酶在细菌炎症中的作用尚不清楚.
研究的目的:
- 为了研究DDX5在细菌引起的炎症中的作用.
- 阐明DDX5调节炎症反应的分子机制.
主要方法:
- 研究了DDX5与METTL3/METTL14复合物的相互作用.
- 分析了TLR2/4mRNA的m6A修饰.
- 在细菌感染时通过全方位素-蛋白酶体通路研究了DDX5降解.
- 在DDX5-和METTL3-淘汰赛小鼠中验证的发现.
主要成果:
- DDX5与METTL3/METTL14形成一个m6A写字复合体,促进TLR2/4mRNA衰变并减少它们的表达.
- 细菌感染引发DDX5降解,导致TLR2/4表达和NF-κB激活的增加.
- 淘汰DDX5和METTL3的小鼠表现出增强的炎症性细胞因子表达.
结论:
- 在细菌感染期间,DDX5充当调节炎症的分子开关.
- DDX5通过m6A修改控制TLR2/4mRNA的稳定性.
- 破坏DDX5介导途径在细菌挑战期间促进炎症.
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