基于酶解的RNA pull-down确定了YTHDC2作为抗病毒先天反应的抑制剂
Jun Zhu1, Shuo Liu2, Jiali Fang3
1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; Frontier Research Center for Cell Response, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Cell reports
|September 30, 2023
概括
研究人员确定YT521-B同源域含有2 (YTHDC2) 是终止先天免疫反应的关键调节者. YTHDC2降解干扰素βmRNA,防止病毒感染后的长期炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 及时终止先天免疫反应对于防止晚期感染期间过度炎症至关重要.
- 在这个终结过程中,m6A修饰RNA及其相关蛋白质的功能在很大程度上仍未被描述.
研究的目的:
- 开发一种用于识别m6A修饰RNA结合蛋白的新方法.
- 阐明m6A修饰的RNA结合蛋白在调节先天免疫反应终结中的作用.
主要方法:
- 开发一种基于酶解的RNA下拉 (eRP) 技术,使用Streptococcus pyogenes IdeS酶.
- 应用eRP捕获和识别与甲基化单链RNA (ssRNA) 探针相关的蛋白质.
- 在体外和体内确定蛋白质功能的验证.
主要成果:
- 确定了YT521-B同源域含有2 (YTHDC2) 作为一个m6A修饰的干扰素-β (IFN-β) mRNA结合蛋白.
- 证明YTHDC2招募IFN刺激的外核酶ISG20来降解IFN-βmRNA,从而抑制抗病毒天生的免疫反应.
- 在晚期病毒感染期间,在YTHDC2缺乏条件下观察到IFN-β产量的增加.
结论:
- 这项研究确立了eRP方法作为发现RNA-蛋白相互作用的有效工具.
- 通过降解IFN-βmRNA,YTHDC2在终止先天免疫反应方面发挥着关键作用.
- 这些发现为通过调节先天性免疫反应终止来维持免疫平衡提供了机制性的见解.
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