Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder.
Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder.
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长非编码RNA：了解酒精使用障碍病因学的新前沿。
DOI：
10.3390/ncrna8040059
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发表时间：
2022-08-04
期刊：
影响因子：
4.3
通讯作者：
Vladimirov, Vladimir I
中科院分区：
文献类型：
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作者：
Denham, Allie N;Drake, John;Gavrilov, Matthew;Taylor, Zachary N;Bacanu, Silviu-Alin;Vladimirov, Vladimir I
酒精使用障碍（AUD）是一种复杂的、慢性的、使人衰弱的疾病，影响着全世界数百万人。已知遗传、环境和表观遗传因素有助于AUD的发展。长链非编码rna （lncRNAs）是一类调控rna，通常被称为基因组的“暗物质”，几乎没有蛋白质编码潜力。lncrna参与了许多对细胞存活至关重要的过程，这表明它们在调节不同的细胞过程中发挥着重要的功能作用。LncRNAs还显示出比蛋白质编码基因更高的组织特异性，并且在大脑和中枢神经系统中具有更高的丰度，这表明在精神疾病的病因学中可能发挥作用。事实上，来自死后脑组织的遗传（如全基因组关联研究（GWAS））、分子（如表达数量性状位点（eQTL））和表观遗传研究已经确定了越来越多与神经精神和物质使用障碍相关的lncrna。考虑到lncRNAs的表达模式与转录组的广泛变化有关，包括甲基化、染色质结构以及翻译活性的激活或抑制，lncRNAs的调控性质可能是普遍存在的，并且是基因调控的先天组成部分。在这篇综述中，我们简要介绍了lncrna在AUD病因学中可能发挥的功能影响。我们还讨论了lncrna的分类、已知的功能作用以及lncrna领域的治疗进展，以进一步阐明lncrna与AUD之间的功能关系。
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.