рибо核酶活动破坏了裸体细胞外RNA的免疫感应
Mauricio Castellano1, Valentina Blanco2, Marco Li Calzi2
1Functional Genomics Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay; Immunoregulation and Inflammation Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay; Analytical Biochemistry Unit, School of Science, Universidad de la República, Montevideo 11400, Uruguay.
Cell genomics
|May 7, 2025
概括
细胞外RNAs (exRNAs) 在没有囊泡的情况下是功能性的. 核糖核酶抑制剂揭示裸体RNA触发了免疫反应和细胞间通信,挑战了以前对exRNA研究的障碍.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 细胞膜传统上被视为阻碍细胞外RNA (exRNA) 吸收的障碍.
- 很少观察到裸体exRNAs的功能性细胞质递送,这阻碍了对其作用的理解.
- 补充剂中的细胞外核糖核酶 (RNases) 可能已经掩盖了对exRNA功能性的研究.
研究的目的:
- 为了研究裸体exRNAs的生物活性和细胞吸收.
- 确定核糖核酶在掩盖exRNA功能中的作用.
- 探索通过裸体exRNA介导的非囊膜细胞间通信的潜力.
主要方法:
- 在细胞培养中利用核糖核酶抑制剂 (RI) 阻止RNase活性.
- 通过托尔类受体 (TLRs) 评估了树突细胞和巨细胞的促炎反应.
- 研究了内分体逃逸和细胞核RNA传感器参与.
- 检查了细胞外mRNAs的内化和翻译.
- 评估了RI联合注射对免疫细胞激活的体内影响.
- 在RNase贫乏环境中测试裸体RNA生物活性.
主要成果:
- 当RNases被抑制时,裸体的exRNAs通过TLRs触发免疫细胞中的促炎反应.
- 裸体的exRNA可以逃离内分泌体并激活细胞质RNA传感器.
- 细胞外mRNA被细胞以RI-依赖的方式内化和翻译.
- 在体内,RI联合注射放大了裸体RNA诱导的免疫细胞激活.
- 裸体RNA在RNase-poor条件下表现出固有的促炎性质.
结论:
- 细胞外核糖核酶掩盖了裸体exRNAs的功能潜力.
- 裸体RNA具有生物活性,可以在没有囊泡封装的情况下调解细胞间通信.
- 这些发现支持一种非膀性exRNA介导通信模型.
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