ArticleeLife2021
FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 59 citations in OpenAlex.
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- Multiplexed smFISH Reveals the Spatial Organization of Neuropil Localized mRNAs Is Linked to Abundance.eNeuro · 2025Article
- FMRP drives mRNP targets into translationally silenced complexes.Molecular cell · 2025Article
- Neuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators.Science advances · 2025Article
- ErbB inhibition rescues nigral dopamine neuron hyperactivity and repetitive behaviors in a mouse model of fragile X syndrome.Molecular psychiatry · 2025Article
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- How energy determines spatial localisation and copy number of molecules in neurons.Nature communications · 2025Article
- Construction destruction: Contribution of dyregulated proteostasis to neurodevelopmental disorders.Current opinion in neurobiology · 2025Review
- Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation.bioRxiv : the preprint server for biology · 2025Article
- Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome.Frontiers in pharmacology · 2025Article
- Reelin signaling as a translational rheostat: linking synaptic homeostasis to neurodevelopment and neurodegeneration.Frontiers in molecular neuroscience · 2025Article
- Navigating a complex dance: the interplay between RNA-binding proteins and T cells in oral epithelial plasticity.Immunometabolism (Cobham, Surrey) · 2025Review
- FMRP regulates MFF translation to locally direct mitochondrial fission in neurons.Nature cell biology · 2024Article
- Deep functional measurements of Fragile X syndrome human neurons reveal multiparametric electrophysiological disease phenotype.Communications biology · 2024Article
- Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes.American journal of human genetics · 2024Article
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9 authors at 2 institutions in 1 country.
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Abstract
Neurons rely on translation of synaptic mRNAs in order to generate activity-dependent changes in plasticity. Here, we develop a strategy combining compartment-specific crosslinking immunoprecipitation (CLIP) and translating ribosome affinity purification (TRAP) in conditionally tagged mice to precisely define the ribosome-bound dendritic transcriptome of CA1 pyramidal neurons. We identify CA1 dendritic transcripts with differentially localized mRNA isoforms generated by alternative polyadenylation and alternative splicing, including many that have altered protein-coding capacity. Among dendritic mRNAs, FMRP targets were found to be overrepresented. Cell-type-specific FMRP-CLIP and TRAP in microdissected CA1 neuropil revealed 383 dendritic FMRP targets and suggests that FMRP differentially regulates functionally distinct modules in CA1 dendrites and cell bodies. FMRP regulates ~15-20% of mRNAs encoding synaptic functions and 10% of chromatin modulators, in the dendrite and cell body, respectively. In the absence of FMRP, dendritic FMRP targets had increased ribosome association, consistent with a function for FMRP in synaptic translational repression. Conversely, downregulation of FMRP targets involved in chromatin regulation in cell bodies suggests a role for FMRP in stabilizing mRNAs containing stalled ribosomes in this compartment. Together, the data support a model in which FMRP regulates the translation and expression of synaptic and nuclear proteins within different compartments of a single neuronal cell type.
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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.