Researchers have discovered a new mechanism1 that could makes microRNAs (miRNAs) a therapeutic target to treat diseases such as tuberculosis, leishmaniasis and cancer. They have shown how a temporary and reversible repression mediated by miRNA helps the expression of pro-inflammatory genes and prevent pathogen attacks .
In mammalian macrophages (cells which eat up pathogens), the expression of a number of cytokines (immunomodulators) is regulated by miRNAs. When macrophages are activated during a pathogen attack, the cytokine mRNAs are translated into proteins, although the expression of miRNAs targeting such mRNAs remains largely unaltered.
The researchers show that during the early phase of the inflammatory response in macrophages, there is a transient reversal of miRNA-mediated repression. This protects the cytokine mRNAs from miRNA-mediated repression. This occurs through a process called Ago2 phosphorylation.
Macrophages expressing a mutant AGO2 (which remains bound to miRNAs during macrophage activation) have a weak inflammatory response and fail to prevent parasite invasion. The findings highlight the relevance of the transient relief that miRNA repression brings to macrophage function.
