通过DIS3L2介导的RNA监测和细胞外囊泡包装,可以通过异常的细胞RNA阻止先天免疫激活
Sandra G Williams1,2, Soyeong Sim2, Wilfried M Guiblet2,3
1National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892.
概括
细胞外囊泡 (EVs) 包装异常的非编码RNA (ncRNAs),包括碎片和不成熟的形式. 这种包装与DIS3L2的降解相竞争,可能阻止免疫激活.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 细胞外囊泡 (EVs) 越来越多地被认为是它们在细胞间通信中的作用.
- 虽然信息RNA (mRNA) 和microRNA (miRNA) 在EV中得到了广泛的研究,但其他非编码RNA (ncRNA) 更为丰富.
- 在EV中ncRNAs的组成及其功能相关性在很大程度上仍然未知.
研究的目的:
- 来自小鼠和人类细胞的EVs的RNA组件的特征.
- 为了研究包装在EVs中的ncRNAs的性质.
- 探索异常ncRNAs的EV包装,DIS3L2活动和先天免疫反应之间的关系.
主要方法:
- 从细胞培养基中净化EVs.
- 高通量测序和北方涂抹用于分析RNA含量.
- DIS3L2的耗尽和使用中性基胺酶抑制剂的治疗.
主要成果:
- EVs被异常的ncRNA丰富,包括碎片,不成熟的形式和短的内核.
- 许多EV的ncRNA都具有oliguridine尾巴,这是DIS3L2中介降解的标志.
- DIS3L2的耗尽增加了EV的释放和EV中尾巴RNA的比例,这表明降解和包装之间的竞争.
- 在DIS3L2枯竭时发生ISG上调,并通过抑制外体生物生成来增强,与异常ncRNA积累相关.
结论:
- EVs包装了相当一部分异常的ncRNAs.
- 异常ncRNAs的EV包装作为一种防止它们在细胞内积累和随后激活先天免疫传感器的机制.
- DIS3L2介导衰变和EV包装代表了处理有缺陷的ncRNAs的竞争途径.
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