Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
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DOI:
10.1038/ncb1596
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发表时间:
2007-06-01
影响因子:
21.3
通讯作者:
Lotvall, Jan O.
Lotvall, Jan O.
中科院分区:
生物学1区
文献类型:
--
作者:
Valadi, Hadi;Ekstrom, Karin;Lotvall, Jan O.

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外切小体是许多细胞释放的内吞来源的囊泡。这些小泡可以调节细胞之间的通讯,促进抗原呈递等过程。在这里,我们展示了来自小鼠和人类肥大细胞系(分别为MC/9和HMC-1)的外体,以及原代骨髓来源的小鼠肥大细胞含有RNA。微阵列评估显示,大约有1300个基因的信使核糖核酸存在,其中许多不存在于供体细胞的细胞质中。体外翻译证明外体mRNAs具有功能。对来自外切体的总RNA进行质量控制RNA分析也发现存在小RNA,包括microRNAs。肥大细胞外切体中的RNA可以移植到其他小鼠和人类肥大细胞中。将小鼠外体RNA转移到人肥大细胞后,在受体细胞中发现了新的小鼠蛋白,这表明所转移的外体RNA进入另一个细胞后可以被翻译。综上所述,我们发现外切体同时含有mRNA和microRNA,它们可以被传递到另一个细胞,并在这个新的位置上发挥功能。我们建议将这种RNA称为“外体穿梭RNA”(EsRNA)。
Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).