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Chunk #40 — MIRNAS AS A MECHANISM OF POST-TRANSCRIPTIONAL REGULATION BY CHRONIC ETHANOL

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Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain.
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Two recent, still unpublished, studies have concomitantly examined expression levels of protein-coding genes and miRNAs in the medial prefrontal cortex of Wistar rats exposed to 7 weeks of chronic intermittent inhalation of ethanol vapors, and sacrificed 3 weeks into withdrawal. A first study used an oligonucleotide array, along with a small non-coding RNA array [34, and personal communication from J. Tapocik]. A total of 165 genes were differentially expressed during protracted abstinence, and over-represented functional categories included myelination, ion channels, synaptic transmission and synaptic plasticity. An integrative analysis of the small and whole transcriptome datasets identified 33 miRNAs targeting 89 genes that were regulated in opposite directions. In particular, miR-9 was hypothesized to down-regulate 10 target genes. A second study used high-throughput sequencing to expand the range of profiled transcripts [33, and personal communication from J. Tapocik]. A total of 783 mRNAs and 861 small RNAs were differentially expressed in post-dependent animals. Network analysis highlighted interconnected genes involved in neurotransmission and signal transduction, and miRNAs miR-133b, miR-292-5p and miR-200 were hypothesized to orchestrate the regulation of this network.