Expression of the neuronal tRNA n-Tr20 regulates synaptic transmission and seizure susceptibility

Loss of the nuclear-encoded brain-specific arginine UCU tRNA, n-Tr20, gene increases seizure threshold in mice, and alters inhibitory neurotransmission in the hippocampus. We investigated the molecular impact of loss of n-Tr20 expression on the trancriptome and translatome in the forebrain and hippocampus of multiple n-Tr20 mutant and control strains. Loss of n-Tr20 altered translation initiation by activating the integrated stress response and suppressing mTOR signaling, the latter of which contributes to the enhanced GABAergic transmission. 33 samples are analyzed in this study from n-Tr20 tRNA knockouts and transgenes in the context of C57BL/6J (B6J) and C57BL6/NJ (B6N) forebrain and hippocampus. The design includes 4 replicates each of forebrain RNA-seq from B6N, B6N-nTr20-/-, B6J-nTr20-/-, B6J, and B6J with the B6N n-Tr20 transgene (B6J-Tg(nTr20N/N) or B6J-Tgwt) mice; one sample was sequenced twice to account for batch effects. Additionally, this study includes hippocampus RNA-seq and ribosome profiling with 3 replicates each from B6N and B6N-nTr20-/- hippocampi.