MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells

Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo to recipient cells to affect the stability of individual mRNAs and the cells’ transcriptome. The exte...

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Veröffentlicht in:PLoS genetics Jg. 17; H. 12; S. e1009951
Hauptverfasser: Albanese, Manuel, Chen, Yen-Fu Adam, Hüls, Corinna, Gärtner, Kathrin, Tagawa, Takanobu, Mejias-Perez, Ernesto, Keppler, Oliver T., Göbel, Christine, Zeidler, Reinhard, Shein, Mikhail, Schütz, Anne K., Hammerschmidt, Wolfgang
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 06.12.2021
Public Library of Science (PLoS)
Schlagworte:
Analysis
Animals
Biology and life sciences
Cell Communication - genetics
Cells
Composition
Extracellular Vesicles - genetics
Flow Cytometry
HEK293 Cells
Humans
Identification and classification
Luciferases - genetics
Medicine and Health Sciences
MicroRNA
MicroRNAs - genetics
Plasmids - genetics
Properties
Research and analysis methods
RNA, Messenger - genetics
Transcriptome - genetics
Transfection
United States
ISSN:1553-7404, 1553-7390, 1553-7404
Online-Zugang:Volltext
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Zusammenfassung:Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo to recipient cells to affect the stability of individual mRNAs and the cells’ transcriptome. The extent to which miRNAs are exported via the EV route and whether they contribute to cell-cell communication are controversial. To address these issues, we defined multiple properties of EVs and analyzed their capacity to deliver packaged miRNAs into target cells to exert biological functions. We applied well-defined approaches to produce and characterize purified EVs with or without specific viral miRNAs. We found that only a small fraction of EVs carried miRNAs. EVs readily bound to different target cell types, but EVs did not fuse detectably with cellular membranes to deliver their cargo. We engineered EVs to be fusogenic and document their capacity to deliver functional messenger RNAs. Engineered fusogenic EVs, however, did not detectably alter the functionality of cells exposed to miRNA-carrying EVs. These results suggest that EV-borne miRNAs do not act as effectors of cell-to-cell communication.
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These authors share first authorship on this work.
Current address: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
The authors have declared that no competing interests exist.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1009951