title: Immediate-early alcohol-responsive miRNA expression in Drosophila.
abstract: At the core of the changes characteristic of alcoholism are alterations in gene expression in the brain of the addicted individual. These changes are believed to underlie some of the neuroadaptations that promote compulsive drinking. Unfortunately, the mechanisms by which alcohol consumption produces changes in gene expression remain poorly understood. MicroRNAs (miRNAs) have emerged as important regulators of gene expression because they can coordinately modulate the translation efficiency of large sets of specific mRNAs. Here, we investigate the early miRNA responses elicited by an acute sedating dose of alcohol in the Drosophila model organism. In our analysis, we combine the power of next-generation sequencing with Drosophila genetics to identify alcohol-sensitive miRNAs and to functionally test them for a role in modulating alcohol sensitivity. We identified 14 known Drosophila miRNAs, and 13 putative novel miRNAs that respond to an acute sedative exposure to alcohol. Using the GeneSwitch Gal4/UAS system, a subset of these ethanol-responsive miRNAs was functionally tested to determine their individual contribution in modulating ethanol sensitivity. We identified two microRNAs that when overexpressed significantly increased ethanol sensitivity: miR-6 and miR-310. MicroRNA target prediction analysis revealed that the different alcohol-responsive miRNAs target-overlapping sets of mRNAs. Alcoholism is the product of accumulated cellular changes produced by chronic ethanol consumption. Although all of the changes described herein are extremely rapid responses evoked by a single ethanol exposure, understanding the gene expression changes that occur in the first few minutes after ethanol exposure will help us to categorize ethanol responses into those that are near instantaneous and those that are emergent responses produced only by repeated ethanol exposure.
authors.affiliation: a Department of Biology , University of Puerto Rico , Rio Piedras, San Juan , Puerto Rico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ghezzi
authors.affiliation: b Department of Neuroscience and Waggoner Center for Alcohol and Addiction Research , The University of Texas at Austin , Austin , TX , USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Zomeno
authors.affiliation: c The Biologically Inspired Neural and Dynamical Systems (BINDS) Lab, Department of Computer Science , University of Massachusetts Amherst , Amherst , MA , USA.
authors.forename: Andrzej Z
authors.initials: AZ
authors.lastname: Pietrzykowski
authors.affiliation: b Department of Neuroscience and Waggoner Center for Alcohol and Addiction Research , The University of Texas at Austin , Austin , TX , USA.
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Atkinson
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D004331:Drosophila melanogaster; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D035683:MicroRNAs; D000431:Ethanol
keywords: Alcoholism; genomics; miR-310; miR-6; miRNA-seq; neuroadaptation