Regulation of impulsive and aggressive behaviours by a novel lncRNA

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.

Automated summary

High levels of impulsivity and aggressiveness are associated with poor behavioral control, and the molecular mechanisms underlying these traits are not well understood. A newly identified long noncoding RNA, named MAOA-associated lncRNA (MAALIN), has been found to regulate the expression of the MAOA gene in the brain, impacting impulsive and aggressive behaviors through epigenetic mechanisms such as DNA methylation. This study suggests that DNA methylation variations play a role in regulating the expression of MAALIN, affecting MAOA expression and impulsive-aggressive behaviors.