Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells

Cell Rep. 2014 Sep 11;8(5):1432-46. doi: 10.1016/j.celrep.2014.07.035. Epub 2014 Aug 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Communication
  • Cells, Cultured
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Endothelial Cells / metabolism*
  • Exosomes / metabolism*
  • Macrophages / metabolism*
  • Mice
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Multivesicular Bodies / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism


  • MicroRNAs
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases