Journal ArticleDOI
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
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TLDR
It is shown that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location, and it is proposed that this RNA is called “exosomal shuttle RNA” (esRNA).Abstract:
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).read more
Citations
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Circulating microRNAs as stable blood-based markers for cancer detection
Patrick S. Mitchell,Rachael K. Parkin,Evan M. Kroh,Brian R. Fritz,Brian R. Fritz,Stacia K. Wyman,Era L. Pogosova-Agadjanyan,Amelia Peterson,Jennifer Noteboom,Kathy O'Briant,April Allen,Daniel W. Lin,Daniel W. Lin,Daniel W. Lin,Nicole Urban,Charles W. Drescher,Beatrice S. Knudsen,Derek L. Stirewalt,Robert Gentleman,Robert L. Vessella,Robert L. Vessella,Peter S. Nelson,Daniel Martin,Daniel Martin,Muneesh Tewari +24 more
TL;DR: It is shown here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity and established the measurement of tumor-derived mi RNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
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Extracellular vesicles: exosomes, microvesicles, and friends.
TL;DR: This review focuses on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
Journal ArticleDOI
Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
TL;DR: This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of micro RNA function.
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Shedding light on the cell biology of extracellular vesicles.
TL;DR: Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.
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Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Johan Skog,T. Wurdinger,van Rijn S,Dimphna H. Meijer,Gainche L,Miguel Sena-Esteves,William T. Curry,Bob S. Carter,Anna M. Krichevsky,Xandra O. Breakefield +9 more
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
References
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Journal ArticleDOI
Proteomic Analysis of Dendritic Cell-Derived Exosomes: A Secreted Subcellular Compartment Distinct from Apoptotic Vesicles
Clotilde Théry,Muriel Boussac,Philippe Veron,Paola Ricciardi-Castagnoli,Graça Raposo,Jérôme Garin,Sebastian Amigorena +6 more
TL;DR: Using a systematic proteomic approach, the first extensive protein map of a particular exosome population is established and a novel category of exosomal proteins related to apoptosis is identified: thioredoxin peroxidase II, Alix, 14-3-3, and galectin-3.
Journal ArticleDOI
MicroRNA functions in animal development and human disease
TL;DR: This review will summarise the current knowledge of animal microRNA function and discuss the emerging links of microRNA biology to stem cell research and human disease, in particular cancer.
Journal ArticleDOI
Exosomal-like vesicles are present in human blood plasma.
Marie-Pierre Caby,Danielle Lankar,Claude Vincendeau-Scherrer,Graça Raposo,Christian Bonnerot +4 more
TL;DR: It is demonstrated that blood is a physiological fluid for exosome circulation in the body, suggesting their role in cell-cell or organ-organ communications as carriers for molecules that need to reach distant cell targets.
Journal ArticleDOI
Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.
Clotilde Théry,Armelle Regnault,Jérôme Garin,Joseph Wolfers,Laurence Zitvogel,Paola Ricciardi-Castagnoli,Graça Raposo,Sebastian Amigorena +7 more
TL;DR: DC-derived exosomes accumulate a defined subset of cellular proteins reflecting their endosomal biogenesis and accounting for their biological function, and exosome production is downregulated upon DC maturation, indicating that in vivo,Exosomes are produced by immature DCs in peripheral tissues.
Journal ArticleDOI
Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.
Adrian E. Morelli,Adriana T. Larregina,William J. Shufesky,Mara Sullivan,Donna B. Stolz,Glenn D. Papworth,Alan F. Zahorchak,Alison J. Logar,Zhiliang Wang,Simon C. Watkins,Louis D. Falo,Angus W. Thomson +11 more
TL;DR: It is demonstrated that exosomes also are internalized and processed by immature DCs for presentation to CD4(+) T cells, implying that exOSomes present in circulation or extracellular fluids constitute an alternative source of self- or allopeptides for DCs during maintenance of peripheral tolerance or initiation of the indirect pathway of allorecognition in transplantation.
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