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Review
. 2015 Feb;13(1):17-24.
doi: 10.1016/j.gpb.2015.02.001. Epub 2015 Feb 24.

Exosome and exosomal microRNA: trafficking, sorting, and function

Jian Zhang  1 , Sha Li  1 , Lu Li  2 , Meng Li  3 , Chongye Guo  3 , Jun Yao  4 , Shuangli Mi  5
Affiliations
Review

Exosome and exosomal microRNA: trafficking, sorting, and function

Jian Zhang et al. Genomics Proteomics Bioinformatics. 2015 Feb.

Abstract

Exosomes are 40-100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal miRNAs, since the miRNA profiles of exosomes may differ from those of the parent cells. Exosomal miRNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal miRNAs, and briefly describe how exosomes and their miRNAs function in recipient cells. Finally, we will discuss the potential applications of these miRNA-containing vesicles in clinical settings.

Keywords: Cell-to-cell communication; Circulating microRNA; Exosome; Extracellular microRNA; Sorting.

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Figures

Figure 1
Figure 1
The sorting mechanism for exosomal microRNAs In animals, microRNA (miRNA) genes are transcribed into primary miRNAs (pri-miRNAs), and processed by the Drosha complex to form precursor miRNAs (pre-miRNAs), which are exported into the cytoplasm by the exportin5 complex. The pre-miRNAs undergo digestion by the Dicer complex to become mature miRNAs. Mature miRNAs are sorted into exosomes via four potential modes: (1) nSMase2-dependent pathway; (2) miRNA motif and sumoylated hnRNPs-dependent pathway; The sumoylated hnRNP family protein recognizes the GGAG motif in the 3′ portion of the miRNA sequence and guides specific miRNAs to be packed into exosomes. (3) 3′ miRNA sequence-dependent pathway; miRNAs that are preferentially sorted into exosomes have more poly(U) than poly(A) at the 3′ end. (4) The miRISC-related pathway. miRISCs co-localize with the sites of exosome biogenesis (multivesicular bodies) and their components, such as AGO2 protein and miRNA-targeted mRNA, are correlated with sorting of miRNAs into exosomes.
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