ArticleMolecular psychiatry2020
UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Beyond quality control: biological roles of nonsense-mediated RNA decay.The EMBO journal · 2026Review
- Mechanism of action of synaptic mitochondrial damage in delayed cognitive recovery.Neural regeneration research · 2026Article
- Nonsense-mediated mRNA decay and associated splicing patterns in neurodevelopmental disorders.Frontiers in molecular biosciences · 2026Review
- Biological roles of nonsense-mediated RNA decay: insights from the nervous system.Current opinion in genetics & development · 2025Review
- Erasing "bad memories": reversing aberrant synaptic plasticity as therapy for neurological and psychiatric disorders.Molecular psychiatry · 2025Review
- ESC models of autism with copy-number variations reveal cell-type-specific translational vulnerability.Cell genomics · 2025Article
- Cell type- and factor-specific nonsense-mediated RNA decay.Nucleic acids research · 2025Article
- FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells.Genome biology · 2024Review
- RNA in axons, dendrites, synapses and beyond.Frontiers in molecular neuroscience · 2024Review
- Impact of UPF2 on the levels of CD81 on extracellular vesicles.Frontiers in cell and developmental biology · 2024Article
- Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling.Cell reports · 2023Article
- Circular RNA: A novel and potential regulator in pathophysiology of schizophrenia.Metabolic brain disease · 2022Review
- Review
- Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder.Biomedicines · 2022Article
- Article
- NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome.Genome biology · 2021Article
- Article
- Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc.Brain sciences · 2020Article
- Article
- Mechanisms and consequences of subcellular RNA localization across diverse cell types.Traffic (Copenhagen, Denmark) · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
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, memory, spine density, synaptic plasticity (L-LTP), and potentiates perseverative/repetitive behavior in mice. We report that the NMD pathway operates within dendrites to regulate Glutamate Receptor 1 (GLUR1) surface levels. Specifically, UPF2 modulates the internalization of GLUR1 and promotes its local synthesis in dendrites. We identified neuronal Prkag3 mRNA as a mechanistic substrate for NMD that contributes to the UPF2-mediated regulation of GLUR1 by limiting total GLUR1 levels. These data establish that UPF2 regulates synaptic plasticity, cognition, and local protein synthesis in dendrites, providing fundamental insight into the neuron-specific function of NMD within the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.