Epitranscriptomic and Metabolomic Signatures Involved in Translational Mechanisms of Suicide and Depression

Abstract

RNA cytosine methylation (m5C) is a novel epigenetic modification only recently characterized in mammalian tissue and most abundant in tRNAs. We recently showed that dysregulation of cortical NSUN2, a tRNA methyltransferase, induces bi-directional effects on tRNA methylation and depressive-like behavior through alterations in translational dynamics of Glycine (Gly)-rich synaptic proteins in mouse brain, suggesting that tRNA regulation may be an unexplored mechanism of translational control relevant to depression and suicide in the clinical population. Here, we investigated tRNA dysregulation and amino acid metabolomics in post-mortem brain samples from patients who died by suicide during an episode of major depressive disorder (MDD).