A tRNA Variant Translates Into Seizure Resistance
Autor: | Matthew C. Weston |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Genetics business.industry Neurotransmission Current Literature in Basic Science Article 03 medical and health sciences Seizure susceptibility 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure nervous system Transfer RNA Medicine Neurology (clinical) Neuron business 030217 neurology & neurosurgery |
Zdroj: | Neuron Epilepsy Currents |
ISSN: | 1535-7597 |
Popis: | Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility Kapur M, Ganguly A, Nagy G, Adamson SI, Chuang JH, Frankel WN, Ackerman SL. Neuron. 2020;108(1):193-208. e9. doi:10.1016/j.neuron.2020.07.023; PMID: 32853550; PMCID: PMC7572898The 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. |
Databáze: | OpenAIRE |
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