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- W2067381654 abstract "Tolerance represents a critical component of addiction. The large-conductance calcium- and voltage-activated potassium channel (BK) is a well-established alcohol target, and an important element in behavioral and molecular alcohol tolerance. We tested whether microRNA, a newly discovered class of gene expression regulators, plays a role in the development of tolerance. We show that in adult mammalian brain, alcohol upregulates microRNA miR-9 and mediates posttranscriptional reorganization in BK mRNA splice variants by miR-9-dependent destabilization of BK mRNAs containing 3'UTRs with a miR-9 Recognition Element (MRE). Different splice variants encode BK isoforms with different alcohol sensitivities. Computational modeling indicates that this miR-9-dependent mechanism contributes to alcohol tolerance. Moreover, this mechanism can be extended to include regulation of additional miR-9 targets relevant to alcohol abuse. Our results describe a mechanism of multiplex regulation of stability of alternatively spliced mRNA by microRNA in drug adaptation and neuronal plasticity." @default.
- W2067381654 created "2016-06-24" @default.
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- W2067381654 creator A5078018381 @default.
- W2067381654 creator A5090911170 @default.
- W2067381654 date "2008-07-01" @default.
- W2067381654 modified "2023-10-18" @default.
- W2067381654 title "Posttranscriptional Regulation of BK Channel Splice Variant Stability by miR-9 Underlies Neuroadaptation to Alcohol" @default.
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- W2067381654 doi "https://doi.org/10.1016/j.neuron.2008.05.032" @default.
- W2067381654 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2714263" @default.
- W2067381654 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18667155" @default.
- W2067381654 hasPublicationYear "2008" @default.
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