A transient reversal of miRNA-mediated repression controls macrophage activation

Mazumder, Anup ; Bose, Mainak ; Chakraborty, Abhijit ; Chakrabarti, Saikat ; Bhattacharyya, Suvendra N. (2013) A transient reversal of miRNA-mediated repression controls macrophage activation EMBO reports, 14 (11). pp. 1008-1016. ISSN 1469-221X

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Official URL: http://embor.embopress.org/content/14/11/1008

Related URL: http://dx.doi.org/10.1038/embor.2013.149

Abstract

In mammalian macrophages, the expression of a number of cytokines is regulated by miRNAs. Upon macrophage activation, proinflammatory cytokine mRNAs are translated, although the expression of miRNAs targeting these mRNAs remains largely unaltered. We show that there is a transient reversal of miRNA‐mediated repression during the early phase of the inflammatory response in macrophages, which leads to the protection of cytokine mRNAs from miRNA‐mediated repression. This derepression occurs through Ago2 phosphorylation, which results in its impaired binding to miRNAs and to the corresponding target mRNAs. Macrophages expressing a mutant, non‐phosphorylatable AGO2—which remains bound to miRNAs during macrophage activation—have a weakened inflammatory response and fail to prevent parasite invasion. These findings highlight the relevance of the transient relief of miRNA repression for macrophage function.

Item Type:Article
Source:Copyright of this article belongs to EMBO Press.
Keywords:Ago2 Phosphorylation; Lipopolysaccharide; Macrophage Activation; MiRNA; Translational Repression
ID Code:108148
Deposited On:01 Feb 2018 11:12
Last Modified:01 Feb 2018 11:12

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