This review addresses three critical barriers to progress in alcohol research: (1) Regulation of cell function often occurs at the level of alternative splicing of mRNAs (Hartmann & Valcárcel, 2009; Tazi et al., 2009), and emerging evidence indicates that this can be important for alcohol tolerance (Pietrzykowski et al., 2008), yet we have little information about splicing changes in human alcoholism. This can now be examined using next-generation sequencing of brain RNA from alcoholics and controls. (2) We do not know if our rodent and nonhuman primate models of alcohol consumption or dependence contain any of the molecular signatures found in human alcoholic brain. Because these animal models must serve as the basis for future medication development, it is essential to determine which, if any, display genomic convergence with human alcoholics. (3) Noncoding RNAs (ncRNAs) are emerging as “master regulators” of gene expression and may underlie many of the widespread genomic changes produced by chronic alcohol consumption, yet we have limited knowledge of changes in brain miRNA levels in human alcoholics or animal models and even less is understood regarding the behavioral significance of changes in ncRNAs.
