Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder

Alcohol use disorder (AUD) is a complex, chronic, debilitating condition impacting millions worldwide. Genetic, environmental, and epigenetic factors are known to contribute to the development of AUD. Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs, commonly referred to as the "dark matter" of the genome, with little to no protein-coding potential. LncRNAs have been implicated in numerous processes critical for cell survival, suggesting that they play important functional roles in regulating different cell processes. LncRNAs were also shown to display higher tissue specificity than protein-coding genes and have a higher abundance in the brain and central nervous system, demonstrating a possible role in the etiology of psychiatric disorders. Indeed, genetic (e.g., genome-wide association studies (GWAS)), molecular (e.g., expression quantitative trait loci (eQTL)) and epigenetic studies from postmortem brain tissues have identified a growing list of lncRNAs associated with neuropsychiatric and substance use disorders. Given that the expression patterns of lncRNAs have been associated with widespread changes in the transcriptome, including methylation, chromatin architecture, and activation or suppression of translational activity, the regulatory nature of lncRNAs may be ubiquitous and an innate component of gene regulation. In this review, we present a synopsis of the functional impact that lncRNAs may play in the etiology of AUD. We also discuss the classifications of lncRNAs, their known functional roles, and therapeutic advancements in the field of lncRNAs to further clarify the functional relationship between lncRNAs and AUD.