Pietrzykowski et al (Pietrzykowski et al., 2008)showed that alcohol, acting via a specific miRNA, miR-9, regulates the expression of alternatively spliced mRNAs encoding the large-conductance calcium- and voltage-activated potassium channel (BK), which is a known target of alcohol’s actions in mediating molecular alcohol tolerance. Alcohol caused a rapid up-regulation in miR-9 expression, resulting in selective degradation of BK mRNAs containing a miR-9 target site in their 3′UTRs. The selective degradation of some splice variants but not others altered the profile of BK channels, consistent with the development of tolerance to alcohol (Pietrzykowski et al., 2008). This represents a new mechanism of gene regulation of splice variants that may underlie the neuroadaptive changes that occur at a cellular level to the long-term alcohol exposure.
