Engel M, Chen A
Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Genes Brain Behav. 2018 Mar;17(3):e12428. doi: 10.1111/gbb.12428. Epub 2017 Nov 17.
Covalent RNA modifications were recently rediscovered as abundant RNA chemical tags. Similarly to DNA epigenetic modifications, they have been proposed as essential regulators of gene expression. Here we focus on 3 of the most abundant adenosine methylations: N6-methyladenosine (m A), N6,2'-O-dimethyladenosine (m Am) and N1-methyladenosine (m A). We review the potential role of these modifications on mature mRNA in regulating gene expression within the adult brain, nervous system function and normal and pathological behavior. Dynamic mRNA modifications, summarized as the epitranscriptome, regulate transcript maturation, translation and decay, and thus crucially determine gene expression beyond primary transcription regulation. However, the extent of this regulation in the healthy and maladapted adult brain is poorly understood. Analyzing this novel layer of gene expression control in addition to epigenetics and posttranslational regulation of proteins will be highly relevant for understanding the molecular underpinnings of behavior and psychiatric disorders.
共价RNA修饰最近作为丰富的RNA化学标签被重新发现。与DNA表观遗传修饰类似，它们被认为是基因表达的重要调节因子。在这里，我们重点关注3种最丰富的腺苷甲基化：N6-甲基腺苷（m⁶A）、N6,2'-O-二甲基腺苷（m⁶Am）和N1-甲基腺苷（m¹A）。我们综述了这些修饰在成熟mRNA上对成人大脑内基因表达、神经系统功能以及正常和病理行为的潜在作用。动态mRNA修饰，总结为表观转录组，调节转录本的成熟、翻译和降解，因此在初级转录调控之外至关重要地决定了基因表达。然而，在健康和适应不良的成人大脑中这种调控的程度还知之甚少。除了蛋白质的表观遗传学和翻译后调控之外，分析这一新的基因表达控制层面对于理解行为和精神疾病的分子基础将具有高度相关性。
