Review ArticleFunctional transferred DNA within extracellular vesicles
Section snippets
Characterization of EVs
Extracellular vesicles (EVs) are small membrane vesicles, such as exosomes and shedding vesicles, which can be released from almost all cell types, induced by various stimuli or occur spontaneously [1], [2]. Exosomes are small EVs ranging in size between 50 nm and 100 nm in diameter, with a density of 1.10–1.21 g/ml [3]. They are released upon exocytosis of multivesicular bodies (MVBs), triggered by key molecules including sphingolipid ceramide and ALG-2 interacting protein X (ALIX) [1], [4], [5] (
Transferred DNA within EVs
EVs may vary in their formation, size, abundance, and composition, but they often contain abundant transmembrane and cytosolic proteins, mRNAs, miRNAs, and DNAs [4], [12], [13], [14] (Fig. 1). EVs allow the horizontal transfer of borne molecules from one cell to another, which are shed from almost all cell types under both physiological and pathological conditions [1], [4]. Importantly, the transferred components in EVs are functional and can regulate the biological functions of the recipient
Characteristics of DNA in EVs
To reduce the external DNA contamination, isolated EVs are extensively treated with DNase before DNA extraction to remove the DNA exterior to the EVs. External DNase digestion should now be part of the standard procedure when isolating EVs for nucleic acid analysis [26]. Recent studies have shown that both mitochondrial DNA (mtDNA) and chromosomal DNA are found in EVs [27], [28], [29], [30]. Guescini et al. provide evidence that glioblastoma, astrocyte, and myoblast cells release EVs, which
Biological functions of DNA in EVs
The biological functions of EVs include secretion, immunomodulation, coagulation, and intercellular communication, and cell-to-cell communication is focused in many studies. Of the components within EVs, DNA occurs prominently in EVs during cell death or activation. The presence of DNA in plasma EVs from apoptotic cells is accessible to anti-DNA antibody binding, displaying important immunological effects [39]. Further study has shown that the existence of DNAs in EVs that could be transferred
Cardiovascular diseases
The transfer of DNA in EVs from cardiomyocytes can affect the expressions of the identified genes in recipient fibroblasts [27]. This finding indicates that this horizontal DNA transfer may be related to cardiomyopathies. Consistent with the study above, we have found an endogenous promoter of the AT1R, NF-κβ, can be recruited to the transferred AT1R gene in the nucleus, and increase the transcription of AT1R in the recipient VSMCs [22]. The result shows that the transferred AT1R gene by EVs
Future perspectives
The specific interaction of EVs with recipient cells is followed by either direct fusion or programmed endocytosis. The consequences of the interaction are involved in signal transduction and horizontal transfer among cells. Especially, EVs are now recognized to have important roles in the transfer of gene products including RNA and protein, or even DNA. Horizontal gene transfer by EVs is up to recently considered impossible, for the view that the intercellular DNA transfer has often been
Author contribution
This review was drafted by Jin Cai, supervised by Chunyu Zeng, and critical revised by Gengze Wu, Pedro A. Jose, and Chunyu Zeng.
Disclosures
The authors declare no conflict of interest.
Acknowledgments
These studies were supported in part by grants from National Basic Research Program of China (2013CB531104), and National Natural Science Foundation of China (31430043 and 81400332).
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Contributed equally.