рибо核酶活动破坏了裸体细胞外RNA的免疫感应
Mauricio Castellano1,2, Valentina Blanco1, Marco Li Calzi1
1Functional Genomics Laboratory, Institut Pasteur Montevideo, Uruguay.
bioRxiv : the preprint server for biology
|May 7, 2024
概括
细胞外RNA可以在没有封装的情况下运行,挑战以前的障碍. рибо核酶抑制剂揭示了裸体的RNA.
科学领域:
- 免疫学和分子生物学
- 细胞和分子生理学细胞和分子生理学
背景情况:
- 细胞外RNA (exRNA) 的吸收受到血和内体膜的限制.
- 裸体RNA内化和细胞质输送一直是很难证明的.
- 细胞培养基中的细胞外核核糖酶 (RNases) 隐藏了exRNA的功能.
研究的目的:
- 为了研究裸体细胞外RNA的功能潜力.
- 确定核糖核酶抑制剂 (RI) 在exRNA吸收和活性中的作用.
- 探索exRNA细胞间通信的非囊膜机制.
主要方法:
- 用裸体细菌RNA和RI对免疫细胞 (树突细胞,巨细胞) 的治疗.
- 通过托尔类受体 (TLRs) 介导的促炎反应的评估.
- 在各种细胞类型中分析裸体mRNA内化,内体逃生和细胞质翻译.
- 在体内研究涉及RI与裸体exRNA在小鼠的同时注射.
- 在像腹腔腔这样的核糖核酶贫乏环境中评估exRNA生物活性.
主要成果:
- 裸体细菌RNA诱导树突细胞和巨细胞的亲炎性反应,依赖于RI.
- 鼠类细胞的反应主要由内体Toll-like受体进行介导.
- 裸体RNA经历了内体逃生,激活了细胞质传感器,并可以转化为蛋白质.
- RI增强了脏淋巴细胞和骨髓细胞在体内裸体exRNA的激活.
- 裸体exRNA在缺乏核糖核酶的区间内本质上是促炎的.
结论:
- 裸体细胞外RNA是生物活性,并且能够进行功能性吸收.
- 封装不需要将exRNA输送到细胞中.
- 非膀性exRNA吸收支持细胞间通信和免疫激活.
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