ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
The Role of The RNA Demethylase FTO (Fat Mass and Obesity-Associated) and mRNA Methylation in Hippocampal Memory Formation.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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126 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
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- Obesity-related RNA mJournal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Exercise, Demethylase FTO, Neurological Disorders, and Neuropathic Pain: Potential Molecular Mechanisms.CNS neuroscience & therapeutics · 2026Review
- m6A RNA methylation in neural plasticity, brain aging, and neurodegenerative vulnerability.Molecular brain · 2026Review
- Emerging role of N6-methyladenosine (m6A) epitranscriptomic changes in adult anxiety after adolescent alcohol exposure.Neuropharmacology · 2026Article
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- Rewriting the brain: m6A RNA methylation as an emerging epitranscriptomic regulator in major depressive disorder.Frontiers in molecular neuroscience · 2026Review
- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- Inhibition of N6-Methyladenosine Accumulation by Targeting METTL3 Mitigates Tau Pathology and Cognitive Decline in Alzheimer's Disease.Research square · 2025Article
- Enhanced Protein Synthesis and Hippocampus-Dependent Memory via Inhibition of YTHDF2-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- N6-methyladenosine RNA methylation is a novel epitranscriptomic regulator of excessive alcohol drinking and vulnerability to relapse.bioRxiv : the preprint server for biology · 2025Article
- Local Protein Synthesis at Synapses: A Driver for Synapse Diversification.Journal of neurochemistry · 2025Review
- RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.Journal of advanced research · 2025Review
- Decoding the role of mNeurochemistry international · 2025Review
- N6-methyladenosine RNA modification regulates microglial phagocytosis in the APP/PS1 mouse model of Alzheimer's disease.Genes and immunity · 2025Article
- Epitranscriptomic shifts in M6A RNA methylation influencing transcriptional dynamics in the prefrontal cortex of chronic restraint stress rats.Neurochemistry international · 2025Article
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66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formation of long-lasting memories requires coordinated changes in gene expression and protein synthesis. Although many studies implicate DNA modifications (DNA methylation, histone modifications) in memory formation, the contributions of RNA modifications remain largely unexplored. Here we investigated the role of mRNA methylation in hippocampal-dependent memory formation in mice. RNA modifications are highly dynamic and readily reversible. Methyltransferases add a methyl group to mRNA while demethylases remove methyl groups. Here we focused on examining the role of the best characterized RNA demethylase, FTO (fat mass and obesity-associated) in memory. We observed that FTO is expressed in the nuclei, dendrites and near dendritic spines of mouse dorsal hippocampal CA1 neurons. Next, we found that contextual fear conditioning transiently (0.5 h) decreased Fto levels in these neurons, with the largest decrease in FTO observed near synapses. The decrease in FTO observed shortly after contextual fear conditioning suggests that FTO normally constrains memory formation. To directly test this, we artificially decreased FTO levels in dorsal hippocampus of otherwise normal (wild-type) mice by microinjecting before training a single herpes simplex virus (HSV) vector expressing either CRISPR/Cas9 or shRNA targeted against Fto. Decreasing FTO using either method specifically enhanced contextual fear memory. Together, these results show the importance of FTO during memory formation and, furthermore, implicate mRNA modification and epi-transcriptomics as novel regulators of memory formation.
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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.