Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family

MicroRNAs (miRNAs) have recently emerged as important regulators of ion channel expression. We show here that select miR-106b family members repress the expression of the KCNQ2 K+ channel protein by binding to the 3'-untranslated region of KCNQ2 messenger RNA. During the first few weeks after birth, the expression of miR-106b family members rapidly decreases, whereas KCNQ2 protein level inversely increases. Overexpression of miR-106b mimics resulted in a reduction in KCNQ2 protein levels. Conversely, KCNQ2 levels were up-regulated in neurons transfected with antisense miRNA inhibitors. By constructing more specific and stable forms of miR-106b controlling systems, we further confirmed that overexpression of precursor-miR-106b-5p led to a decrease in KCNQ current density and an increase in firing frequency of hippocampal neurons, while tough decoy miR-106b-5p dramatically increased current density and decreased neuronal excitability. These results unmask a regulatory mechanism of KCNQ2 channel expression in early postnatal development and hint at a role for miR-106b up-regulation in the pathophysiology of epilepsy.

Automated summary

Recently emerged miRNAs, specifically the miR-106b family members, have been found to regulate the expression of the KCNQ2 K+ channel protein by binding to its mRNA. The levels of miR-106b decrease while KCNQ2 protein levels increase after birth. Overexpression of miR-106b leads to reduced KCNQ2 protein levels, while inhibition of miR-106b results in increased levels of KCNQ2.