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

Abstract：

: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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Squadrito ML,Baer C,Burdet F,Maderna C,Gilfillan GD,Lyle R,Ibberson M,De Palma M

doi

10.1016/j.celrep.2014.07.035

subject

Has Abstract

pub_date

2014-09-11 00:00:00

pages

1432-46

issue

5

issn

2211-1247

pii

S2211-1247(14)00619-6

journal_volume

8

pub_type

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