The Epitranscriptomic Effects of Early Life Stress on m6A Regulation Across Brain Reward Circuitry

Abstract

Early life stress refers to ‘chronic and/or extreme stress in early life’, and has been associated with a multitude of negative and persistent effects on ‘prefrontal–hypothalamic–amygdala and dopaminergic circuits’ (Smith & Pollak, 2020). However, the molecular mechanisms underlying these effects have yet to be fully elucidated. Researchers continue to investigate the biological mechanisms responsible for these adverse effects as both ELS and adult stress have been shown to alter the transcriptome. The most abundant RNA modification, N6-methyladenosine (m6A) methylation, refers to the methylation of the adenosine base at the nitrogen-6 position within RNA (Jiang, 2021). This modification plays a crucial role in a variety of biological processes by influencing RNA metabolism and gene expression, and it is recognized by proteins called ‘readers’ which initiate a signal cascade. This research project evaluated how levels of m6A readers are affected by ELS, with the secondary aim of determining whether sex is a factor affecting m6A reader expression. The goal is to provide a deeper understanding of the role that m6A transcriptomic alterations play in the biology behind psychological disorders such as anxiety and depression.