title: A transient reversal of miRNA-mediated repression controls macrophage activation.
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.
authors.affiliation: RNA Biology Research Laboratory, Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.
authors.forename: Anup
authors.initials: A
authors.lastname: Mazumder
authors.forename: Mainak
authors.initials: M
authors.lastname: Bose
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Saikat
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Suvendra N
authors.initials: SN
authors.lastname: Bhattacharyya
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D035683:MicroRNAs; D019000:Phosphotyrosine
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