biostudies-literatureTian YHHS | NIH | National Institute of Mental HealthNIMH NIH HHS1282-1309https://www.ebi.ac.uk/biostudies/studies/S-EPMC10933332biostudies-literatureUnknown25(3)UBE3A is a common genetic factor in ASD etiology, and transgenic mice overexpressing UBE3A exhibit typical autistic-like behaviors. Because AMPA receptors (AMPARs) mediate most of the excitatory synaptic transmission in the brain, and synaptic dysregulation is considered one of the primary cellular mechanisms in ASD pathology, we investigate here the involvement of AMPARs in UBE3A-dependent ASD. We show that expression of the AMPAR GluA1 subunit is decreased in UBE3A-overexpressing mice, and that AMPAR-mediated neuronal activity is reduced. GluA1 mRNA is trapped in the nucleus of UBE3A-overexpressing neurons, suppressing GluA1 protein synthesis. Also, SARNP, an mRNA nuclear export protein, is downregulated in UBE3A-overexpressing neurons, causing GluA1 mRNA nuclear retention. Restoring SAREMBO reportsmRNA nuclear retention reduces AMPAR expression and promotes autistic behavior in UBE3A-overexpressing mice.PMC10933332MH079407R21 MH133014R01 MH130600MH133014R01 MH079407MH130600Lin JWTian YYu FMan HYYun EfalsemRNA nuclear retention reduces AMPAR expression and promotes autistic behavior in UBE3A-overexpressing mice.UBE3A is a common genetic factor in ASD etiology, and transgenic mice overexpressing UBE3A exhibit typical autistic-like behaviors. Because AMPA receptors (AMPARs) mediate most of the excitatory synaptic transmission in the brain, and synaptic dysregulation is considered one of the primary cellular mechanisms in ASD pathology, we investigate here the involvement of AMPARs in UBE3A-dependent ASD. We show that expression of the AMPAR GluA1 subunit is decreased in UBE3A-overexpressing mice, and that AMPAR-mediated neuronal activity is reduced. GluA1 mRNA is trapped in the nucleus of UBE3A-overexpressing neurons, suppressing GluA1 protein synthesis. Also, SARNP, an mRNA nuclear export protein, is downregulated in UBE3A-overexpressing neurons, causing GluA1 mRNA nuclear retention. Restoring SAR2024-01-01T00:00:00Z2024 Mar2026-07-15T16:14:49.488Z2025-04-06T14:32:09.886ZS-EPMC109333323831690010.1038/s44319-024-00073-1