Abstract：
: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.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Labonté B,Abdallah K,Maussion G,Yerko V,Yang J,Bittar T,Quessy F,Golden SA,Navarro L,Checknita D,Gigek C,Lopez JP,Neve RL,Russo SJ,Tremblay RE,Côté G,Meaney MJ,Mechawar N,Nestler EJ,Turecki Gdoi
10.1038/s41380-019-0637-4subject
Has Abstractpub_date
2020-01-06 00:00:00eissn
1359-4184issn
1476-5578pii
10.1038/s41380-019-0637-4pub_type
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