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Chunk #22 — Epigenetics and tolerance: MicroRNA mediates a selective degradation of BK isoforms leading to tolerance

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BK Channels: mediators and models for alcohol tolerance.
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This mechanism of subtractive isoform reorganization (i.e. the loss of sensitive isoforms) is possible because only some of the BK α-subunit mRNAs within a neuron contain 3’UTRs with a miR-9 Recognition Element (MRE). It is only this subset of BK message that is downregulated by alcohol exposure (Figure 3b). Moreover, this mechanism results in the regulation of additional miR-9 targets relevant to alcohol abuse. Thus, one can envision a concept of miRNA master switches, activated by alcohol, coordinating an integrated and dynamic response pattern among a number of downstream targets.