ArticleProceedings of the National Academy of Sciences of the United States of America2015
A 3' untranslated region variant in FMR1 eliminates neuronal activity-dependent translation of FMRP by disrupting binding of the RNA-binding protein HuR.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. 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, 31 citations in OpenAlex.
- The Role of mRNA Alternative Processing in Mammalian Neurodevelopment.International journal of molecular sciences · 2025Review
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.Cell reports · 2024Article
- FMRP phosphorylation and interactions with Cdh1 regulate association with dendritic RNA granules and MEF2-triggered synapse elimination.Neurobiology of disease · 2023Article
- Functional characterization of human genomic variation linked to polygenic diseases.Trends in genetics : TIG · 2023Review
- Development of single-molecule ubiquitination mediated fluorescence complementation to visualize protein ubiquitination dynamics in dendrites.Cell reports · 2022Article
- Beyond Trinucleotide Repeat Expansion in Fragile X Syndrome: Rare Coding and Noncoding Variants inGenes · 2021Article
- Evolution of the Neocortex Through RNA-Binding Proteins and Post-transcriptional Regulation.Frontiers in neuroscience · 2021Review
- The Use of Peptides in the Treatment of Fragile X Syndrome: Challenges and Opportunities.Frontiers in psychiatry · 2021Article
- Reactivation of FMR1 gene expression is a promising strategy for fragile X syndrome therapy.Gene therapy · 2020Review
- A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis.Nature neuroscience · 2020Article
- Prevalence and architecture of posttranscriptionally impaired synonymous mutations in 8,320 genomes across 22 cancer types.Nucleic acids research · 2020Article
- Non-coding RNA in Fragile X Syndrome and Converging Mechanisms Shared by Related Disorders.Frontiers in genetics · 2019Review
- Autism spectrum disorder: insights into convergent mechanisms from transcriptomics.Nature reviews. Genetics · 2019Review
- Aberrant RNA translation in fragile X syndrome: From FMRP mechanisms to emerging therapeutic strategies.Brain research · 2018Review
- Choice of Alternative Polyadenylation Sites, Mediated by the RNA-Binding Protein Elavl3, Plays a Role in Differentiation of Inhibitory Neuronal Progenitors.Frontiers in cellular neuroscience · 2018Article
- HuR (Elavl1) and HuB (Elavl2) Stabilize Matrix Metalloproteinase-9 mRNA During Seizure-Induced Mmp-9 Expression in Neurons.Frontiers in neuroscience · 2018Article
- Identification of a potential functional single nucleotide polymorphism for fatness and growth traits in the 3'-untranslated region of theJournal of animal science · 2017Article
- A novel mechanism for variable phenotypic expressivity in Mendelian diseases uncovered by an AU-rich element (ARE)-creating mutation.Genome biology · 2017Article
- The roles of RNA processing in translating genotype to phenotype.Nature reviews. Molecular cell biology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Fragile X syndrome is a common cause of intellectual disability and autism spectrum disorder. The gene underlying the disorder, fragile X mental retardation 1 (FMR1), is silenced in most cases by a CGG-repeat expansion mutation in the 5' untranslated region (UTR). Recently, we identified a variant located in the 3'UTR of FMR1 enriched among developmentally delayed males with normal repeat lengths. A patient-derived cell line revealed reduced levels of endogenous fragile X mental retardation protein (FMRP), and a reporter containing a patient 3'UTR caused a decrease in expression. A control reporter expressed in cultured mouse cortical neurons showed an expected increase following synaptic stimulation that was absent when expressing the patient reporter, suggesting an impaired response to neuronal activity. Mobility-shift assays using a control RNA detected an RNA-protein interaction that is lost with the patient RNA, and HuR was subsequently identified as an associated protein. Cross-linking immunoprecipitation experiments identified the locus as an in vivo target of HuR, supporting our in vitro findings. These data suggest that the disrupted interaction of HuR impairs activity-dependent translation of FMRP, which may hinder synaptic plasticity in a clinically significant fashion.
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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.