Regulatory function of microRNAs in microglia

Microglia are CNS-resident cells involved in immune surveillance and maintenance of intercellular homeostasis, while also contributing to neurologic pathologies. MicroRNAs (miRNAs) are a class of small (~22 nucleotides) single-stranded noncoding RNAs that participate in gene regulation at the post-transcriptional level. miRNAs typically bind to the untranslated region (3' UTR) of RNAs. It has been shown that miRNAs are important players in controlling inflammation and that their abnormal expression is linked to cancer and ageing, and to the onset and progression of neurodegenerative disease. Furthermore, miRNAs participate in intercellular trafficking. Thus, miRNAs are released from cells in a free form, bound to proteins or packaged within extracellular vesicles (EVs), exerting paracrine and long distance signaling. In this review, recent findings on the role of miRNAs as drivers of microglia phenotypic changes and their cotribution in neurological disease are addressed. MAIN POINTS: miRNAs have a key role in microglia function/dysfunction, polarization, and restoration. Microglia are both a source and recipient of extracellular vesicles (EVs) containing miRNAs. Extracellular miRNAs may be found as soluble (free and EV cargo) and protein complexes.