High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterized a novel long noncoding RNA (lncRNA), acting as a regulator of the monoamine oxidase A (MAOA) gene in the brain, and named it MAOA-associated lncRNA (MAALIN). Our results show that in the brain of suicide completers, MAALIN is regulated by a combination of epigenetic mechanisms including DNA methylation and chromatin modifications. Elevated MAALIN in the dentate gyrus of impulsive-aggressive suicides was associated with lower MAOA expression. Viral overexpression of MAALIN in neuroprogenitor cells decreased MAOA expression while CRISPR-mediated knock out resulted in elevated MAOA expression. Using viral-mediated gene transfer, we confirmed that MAALIN in the hippocampus significantly decreases MAOA expression and exacerbates the expression of impulsive-aggressive behavioural traits in CD1 aggressive mice. Overall, our findings suggest that variations in DNA methylation mediate the differential expression of a novel lncRNA that acts on MAOA expression to regulate impulsive-aggressive behaviours.

中文翻译：

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一种新型 lncRNA 对冲动和攻击行为的调节。

高度冲动和攻击性特征与行为自控能力差有关。尽管它们在预测包括自杀在内的负面行为结果方面很重要，但人们对冲动和攻击性特征表达背后的分子机制仍知之甚少。在这里，我们鉴定并表征了一种新型长链非编码 RNA (lncRNA)，作为大脑中单胺氧化酶 A (MAOA) 基因的调节剂，并将其命名为 MAOA 相关 lncRNA (MAALIN)。我们的研究结果表明，在完成自杀者的大脑中，MAALIN 受表观遗传机制的组合调控，包括 DNA 甲基化和染色质修饰。冲动攻击性自杀的齿状回中升高的 MAALIN 与较低的 MAOA 表达相关。MAALIN 在神经祖细胞中的病毒过表达降低了 MAOA 表达，而 CRISPR 介导的敲除导致 MAOA 表达升高。使用病毒介导的基因转移，我们证实海马体中的 MAALIN 显着降低 MAOA 表达并加剧 CD1 攻击性小鼠的冲动攻击行为特征的表达。总体而言，我们的研究结果表明，DNA 甲基化的变化介导了一种新型 lncRNA 的差异表达，该 lncRNA 作用于 MAOA 表达以调节冲动攻击行为。