Grin2b 3’UTR is necessary for synaptic plasticity and spatial learning
Abstract
Spatially precise protein synthesis is critical for synaptic plasticity and cognitive function. The GRIN2B transcript encodes the GluN2B subunit of N-methyl-D-aspartate (NMDA) receptors and has a 25 kb-long 3’-untranslated region (3’UTR) of unknown function. To investigate its role, we generated a ∆3’UTR mouse line by deleting the Grin2b 3’UTR while preserving the coding sequence. Despite unchanged Grin2b mRNA levels in ∆3’UTR mice, GluN2B protein was reduced 50%. In wildtype (WT) mice, Grin2b mRNA was enriched in synaptosomes, but this enrichment was impaired in ∆3’UTR mice along with reduced GluN2B phosphorylation. Notably, ∆3’UTR mice had no long-term potentiation (LTP) and exhibited hippocampal-dependent spatial learning impairments. Together, these findings demonstrate that the 3’UTR is critical for Grin2b mRNA function, ultimately influencing synaptic composition and plasticity.
Fields of Study & Subjects
Neuroscience and Neuropharmacology Research
Memory and Neural Mechanisms
Amino Acid Enzymes and Metabolism
Publication details
- Journal / source
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Volume
- 123
- Issue
- 8
- Pages
- e2518282123–e2518282123
- Publication date
- 18 February 2026
- Language
- EN