Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility.
Document Type
Article
Publication Date
10-14-2020
Keywords
JGM, JMG, JAXCC
JAX Source
Neuron 2020 Oct 14; 108(1):193-208.e9
Volume
108
Issue
1
First Page
193
Last Page
208
ISSN
1097-4199
PMID
32853550
DOI
https://doi.org/10.1016/j.neuron.2020.07.023
Abstract
The mammalian genome has hundreds of nuclear-encoded tRNAs, but the contribution of individual tRNA genes to cellular and organismal function remains unknown. Here, we demonstrate that mutations in a neuronally enriched arginine tRNA, n-Tr20, increased seizure threshold and altered synaptic transmission. n-Tr20 expression also modulated seizures caused by an epilepsy-linked mutation in Gabrg2, a gene encoding a GABAA receptor subunit. Loss of n-Tr20 altered translation initiation by activating the integrated stress response and suppressing mTOR signaling, the latter of which may contribute to altered neurotransmission in mutant mice. Deletion of a highly expressed isoleucine tRNA similarly altered these signaling pathways in the brain, suggesting that regulation of translation initiation is a conserved response to tRNA loss. Our data indicate that loss of a single member of a tRNA family results in multiple cellular phenotypes, highlighting the disease-causing potential of tRNA mutations.
Recommended Citation
Kapur M,
Ganguly A,
Nagy G,
Adamson S,
Chuang J,
Frankel W,
Ackerman S.
Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility. Neuron 2020 Oct 14; 108(1):193-208.e9