Neuronal Nsun2 Deficiency Is Associated With Codon-Specific Epitranscriptomic Dysregulation Of Gly-Trnas And Corresponding Proteomic Shift Impacting Synaptic Signaling And Behavior

Targeting the brain's translational machinery bears promise for psychiatric disease treatment, but the role of transfer (t)RNAs-- key players for ribosomal protein synthesis-- remains unexplored. RNA cytosine methylation (m5C) is most abundant in tRNAs and plays a regulatory role in protein synthesis. NSUN2, a mammalian tRNA methyltransferase, is expressed at high levels in brain and has been linked to neurodevelopmental defects in humans and mice. Previous work has shown that loss of m5C produces deficits in protein synthesis in non-neuronal cells, but the role of tRNA methylation in adult neuronal function has not been explored.