Oxidative stress-induced changes in the transcriptomic profile of extracellular vesicles

Elizabeth R. Dellar, Claire Hill, David R. F. Carter, Luis Alberto Baena-Lopez
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Abstract

Extracellular vesicles (EVs) have been proposed to play dual roles in cellular homeostasis, functioning both to remove unwanted intracellular molecules, and to enable communication between cells as a means of modulating cellular responses in different physiological and pathological scenarios. EVs contain a broad range of cargoes, including multiple biotypes of RNA, which can vary depending on the cell status, and may function as signalling molecules. In this study, we carried out comparative transcriptomic analysis of Drosophila EVs and cells, demonstrating that the RNA profile of EVs is distinct from cells and shows dose-dependent changes in response to oxidative stress. We identified a high abundance of snoRNAs in EVs, alongside an enrichment of intronic and untranslated regions (UTRs) of mRNAs under stress. We also observed an increase in the relative abundance of either aberrant or modified mRNAs under stress. These findings suggest that EVs may function both for the elimination of specific cellular RNAs, and for the incorporation of RNAs that may hold signalling potential.

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氧化应激诱导的细胞外囊泡转录组图谱变化
细胞外囊泡(EVs)被认为在细胞平衡中扮演着双重角色,既能清除细胞内不需要的分子,又能在不同的生理和病理情况下实现细胞间的交流,作为调节细胞反应的一种手段。EVs含有多种货物,包括多种生物类型的RNA,它们会根据细胞状态的不同而变化,并可能起到信号分子的作用。在这项研究中,我们对果蝇的EV和细胞进行了转录组学比较分析,结果表明EV的RNA谱与细胞不同,并在氧化应激反应中表现出剂量依赖性变化。我们在EVs中发现了高丰度的snoRNAs,同时还发现在压力下mRNAs的内含子区和非翻译区(UTRs)富集。我们还观察到,在应激状态下,异常或修饰的mRNA相对丰度增加。这些研究结果表明,EVs既能消除特定的细胞RNA,也能将可能具有信号潜能的RNA纳入其中。
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