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.  Overall design: 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.