biostudies-literatureNotaras MNIMH NIH HHSNINDS NIH HHS3360-3379https://www.ebi.ac.uk/biostudies/studies/S-EPMC7566522biostudies-literatureUnknown25(12)Synaptic plasticity requires a tight control of mRNA levels in dendrites. RNA translation and degradation pathways have been recently linked to neurodevelopmental and neuropsychiatric diseases, suggesting a role for RNA regulation in synaptic plasticity and cognition. While the local translation of specific mRNAs has been implicated in synaptic plasticity, the tightly controlled mechanisms that regulate local quantity of specific mRNAs remain poorly understood. Despite being the only RNA regulatory pathway that is associated with multiple mental illnesses, the nonsense-mediated mRNA decay (NMD) pathway presents an unexplored regulatory mechanism for synaptic function and plasticity. Here, we show that neuron-specific disruption of UPF2, an NMD component, in adulthood attenuates learning, mMolecular psychiatryUPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.PMC7566522R01 MH114888R29 NS034007R37 NS034007R01 NS047384R01 NS034007Toth MColak DAllen MLi Jeon NVolk NNotaras MLongo FKlann EfalseUPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.Synaptic plasticity requires a tight control of mRNA levels in dendrites. RNA translation and degradation pathways have been recently linked to neurodevelopmental and neuropsychiatric diseases, suggesting a role for RNA regulation in synaptic plasticity and cognition. While the local translation of specific mRNAs has been implicated in synaptic plasticity, the tightly controlled mechanisms that regulate local quantity of specific mRNAs remain poorly understood. Despite being the only RNA regulatory pathway that is associated with multiple mental illnesses, the nonsense-mediated mRNA decay (NMD) pathway presents an unexplored regulatory mechanism for synaptic function and plasticity. Here, we show that neuron-specific disruption of UPF2, an NMD component, in adulthood attenuates learning, m2020-01-01T00:00:00Z2020 Dec2026-05-02T22:53:09.024Z2021-02-20T10:37:41ZS-EPMC75665223163638110.1038/s41380-019-0547-5