Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome.

Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome.
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DOI:
10.1038/s41598-018-28485-9
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发表时间:
2018-07-17
期刊:
影响因子:
4.6
通讯作者:
El Andaloussi S
El Andaloussi S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sork H;Corso G;Krjutskov K;Johansson HJ;Nordin JZ;Wiklander OPB;Lee YXF;Westholm JO;Lehtiö J;Wood MJA;Mäger I;El Andaloussi S

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细胞外囊泡(EV)通过向其受体细胞递送或展示大分子来介导细胞与细胞的通信。虽然某些广谱EV效应反映了它们的蛋白质货物组成,但其他效应归因于单个EV负载分子,如特异性miRNA。在这项工作中,我们使用来自HEK 293 T、RD 4、C2 C12、Neuro 2a和C17.2的细胞和EV的小RNA测序研究了囊泡货物的含量。EV中的大部分RNA含量(49-96%)对应于rRNA、编码和tRNA片段,这与我们对HEK 293 T和C2 C12 EV的蛋白质组学分析相证实,所述分析显示核糖体和抑制相关蛋白的富集。另一方面,囊泡小RNA的总体比例相对较低且可变(2-39%),并且主要由miRNA和定位到皮尔纳基因座的序列组成。重要的是,这是为数不多的研究之一,它系统地连接囊泡RNA和囊泡的蛋白质货物。我们的数据对于未来解开囊泡RNA和蛋白质分选背后的生物学机制特别有用,并且可以作为开发EV作为RNA治疗载体的重要指南。
Extracellular vesicles (EVs) mediate cell-to-cell communication by delivering or displaying macromolecules to their recipient cells. While certain broad-spectrum EV effects reflect their protein cargo composition, others have been attributed to individual EV-loaded molecules such as specific miRNAs. In this work, we have investigated the contents of vesicular cargo using small RNA sequencing of cells and EVs from HEK293T, RD4, C2C12, Neuro2a and C17.2. The majority of RNA content in EVs (49–96%) corresponded to rRNA-, coding- and tRNA fragments, corroborating with our proteomic analysis of HEK293T and C2C12 EVs which showed an enrichment of ribosome and translation-related proteins. On the other hand, the overall proportion of vesicular small RNA was relatively low and variable (2-39%) and mostly comprised of miRNAs and sequences mapping to piRNA loci. Importantly, this is one of the few studies, which systematically links vesicular RNA and protein cargo of vesicles. Our data is particularly useful for future work in unravelling the biological mechanisms underlying vesicular RNA and protein sorting and serves as an important guide in developing EVs as carriers for RNA therapeutics.
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