Journal
CELL REPORTS
Volume 8, Issue 5, Pages 1432-1446Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2014.07.035
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Funding
- Fonds National Suisse de la Recherche Scientifique (SNSF grant) [31003A-143978]
- National Center of Competence in Research (NCCR) in Molecular Oncology
- European Research Council (ERC)
- Anna Fuller Fund
- Swiss Federal Government through the State Secretariat for Education, Research and Innovation (SERI)
- Swiss National Science Foundation (SNF) [31003A_143978] Funding Source: Swiss National Science Foundation (SNF)
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MicroRNA (miRNA) transfer via exosomes may mediate cell-to-cell communication. Interestingly, specific miRNAs are enriched in exosomes in a cell-type-dependent fashion. However, the mechanisms whereby miRNAs are sorted to exosomes and the significance of miRNA transfer to acceptor cells are unclear. We used macrophages and endothelial cells (ECs) as a model of heterotypic cell communication in order to investigate both processes. RNA profiling of macrophages and their exosomes shows that miRNA sorting to exosomes is modulated by cell-activation-dependent changes of miRNA target levels in the producer cells. Genetically perturbing the expression of individual miRNAs or their targeted transcripts promotes bidirectional miRNA relocation from the cell cytoplasm/P bodies (sites of miRNA activity) to multivesicular bodies (sites of exosome biogenesis) and controls miRNA sorting to exosomes. Furthermore, the use of Dicer-deficient cells and reporter lentiviral vectors (LVs) for miRNA activity shows that exosomal miRNAs are transferred from macrophages to ECs to detectably repress targeted sequences.
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