In this paper we demonstrate that, in neurons, several different splice variants of the BK channel α subunit are constructed by combining various concatenations of protein coding exons (e.g. STREX alone, STREX and ALCOREX, ALCOREX alone, INSERTLESS) with different 3’UTRs. Since the 3’UTR serves as a major regulatory element of mRNA expression, stability, turnover and translation efficiency (Garneau et al., 2007; Hughes, 2006), this mechanism allows for BK channel plasticity. We showed that, regardless of partial homology of two BK 3’UTRs, only one of them was regulated by alcohol, due to the selective presence of the miR-9 MRE. These results suggest that even subtle differences in miRNA binding profiles can have profound consequences on gene expression regulation. As many mammalian genes express alternative UTRs (Hughes, 2006), this mechanism of neuronal plasticity is likely to be of great importance in adaptation to many exogenous or endogenous factors. This mechanism might also contribute to alcohol’s effects in humans, since the miR-9 MRE in BK mRNA 3’UTR is conserved between rodents and humans (Figure S9).
