Journal
EMBO REPORTS
Volume 14, Issue 11, Pages 1008-1016Publisher
WILEY
DOI: 10.1038/embor.2013.149
Keywords
Ago2 phosphorylation; lipopolysaccharide; macrophage activation; miRNA; translational repression
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Funding
- WellcomeTrust, UK [084324/Z/07/A]
- CSIR (Council of Scientific and Industrial Research)
- Government of India [BSC 0114]
- Wellcome Trust [084324/Z/07/A] Funding Source: Wellcome Trust
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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.
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