Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.

MicroRNAs (miRNAs) secreted by cells into microvesicles (MVs) form a novel class of signal molecules that mediate intercellular communication. However, several fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism that governs the function or fate of exogenous miRNAs in r...

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Main Authors: Zhiyuan Lv, Yao Wei, Dong Wang, Chen-Yu Zhang, Ke Zen, Limin Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4114802?pdf=render
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author Zhiyuan Lv
Yao Wei
Dong Wang
Chen-Yu Zhang
Ke Zen
Limin Li
author_facet Zhiyuan Lv
Yao Wei
Dong Wang
Chen-Yu Zhang
Ke Zen
Limin Li
author_sort Zhiyuan Lv
collection DOAJ
description MicroRNAs (miRNAs) secreted by cells into microvesicles (MVs) form a novel class of signal molecules that mediate intercellular communication. However, several fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism that governs the function or fate of exogenous miRNAs in recipient cells. In the present study, we provide evidence indicating that Argonaute 2 (Ago2) plays a role in stabilizing miRNAs and facilitating the packaging of secreted miRNAs into MVs. More importantly, Ago2 in origin cell-secreted MVs (but not in recipient cells) directs the function of secreted miRNAs. First, Ago2 overexpression clearly increased the level of miR-16 in cells transfected with a miR-16 mimic by protecting the miRNAs from degradation in lysosomes. Second, Ago2 overexpression increased the level of miR-16 in cell-secreted MVs, suggesting that Ago2 may facilitate the packaging of secreted miRNAs into MVs. Third, exogenous miR-16 delivered by MVs within the origin cells significantly reduced the Bcl2 protein level in recipient cells, and miR-16 and Bcl2 mRNA were physically associated with exogenous HA-tagged Ago2 (HA-Ago2). Finally, the effect of MV-delivered miR-16 on the production of the Bcl2 protein in recipient cells was not abolished by knocking down Ago2 in the recipient cells.
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spelling doaj.art-65ce23f41faf4c828fb33b998d9000372022-12-21T23:53:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10359910.1371/journal.pone.0103599Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.Zhiyuan LvYao WeiDong WangChen-Yu ZhangKe ZenLimin LiMicroRNAs (miRNAs) secreted by cells into microvesicles (MVs) form a novel class of signal molecules that mediate intercellular communication. However, several fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism that governs the function or fate of exogenous miRNAs in recipient cells. In the present study, we provide evidence indicating that Argonaute 2 (Ago2) plays a role in stabilizing miRNAs and facilitating the packaging of secreted miRNAs into MVs. More importantly, Ago2 in origin cell-secreted MVs (but not in recipient cells) directs the function of secreted miRNAs. First, Ago2 overexpression clearly increased the level of miR-16 in cells transfected with a miR-16 mimic by protecting the miRNAs from degradation in lysosomes. Second, Ago2 overexpression increased the level of miR-16 in cell-secreted MVs, suggesting that Ago2 may facilitate the packaging of secreted miRNAs into MVs. Third, exogenous miR-16 delivered by MVs within the origin cells significantly reduced the Bcl2 protein level in recipient cells, and miR-16 and Bcl2 mRNA were physically associated with exogenous HA-tagged Ago2 (HA-Ago2). Finally, the effect of MV-delivered miR-16 on the production of the Bcl2 protein in recipient cells was not abolished by knocking down Ago2 in the recipient cells.http://europepmc.org/articles/PMC4114802?pdf=render
spellingShingle Zhiyuan Lv
Yao Wei
Dong Wang
Chen-Yu Zhang
Ke Zen
Limin Li
Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.
PLoS ONE
title Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.
title_full Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.
title_fullStr Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.
title_full_unstemmed Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.
title_short Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.
title_sort argonaute 2 in cell secreted microvesicles guides the function of secreted mirnas in recipient cells
url http://europepmc.org/articles/PMC4114802?pdf=render
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