Affinage

FMR1

Fragile X messenger ribonucleoprotein 1 · UniProt Q06787

Length
632 aa
Mass
71.2 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FMRP is a polyribosome-associated RNA-binding protein that governs the translation, stability, localization, and transport of a large set of neuronal mRNAs, and its loss underlies the synaptic and neurodevelopmental phenotypes of fragile X syndrome (PMID:12575950, PMID:21784246, PMID:27233938). It uses two KH (RNP) domains that are necessary for polyribosome association and an RGG box that recognizes RNA G-quartet structures, with the protein binding ~4% of brain mRNAs including its own (PMID:7692601, PMID:13130134, PMID:16098133). Mechanistically, FMRP binds predominantly within coding regions and reversibly stalls elongating ribosomes on target transcripts encoding synaptic and autism-linked proteins (PMID:21784246), and it also binds cytoplasmic poly(A)-binding protein to sequester polyadenylated mRNAs into deadenylation-resistant, translationally repressed complexes, so that FMRP loss generally destabilizes targets while increasing protein output per transcript (PMID:36356584). FMRP preferentially stabilizes optimal-codon transcripts and acts in a compartment-specific manner, repressing translation of synaptic mRNAs in dendrites while stabilizing stalled-ribosome transcripts in cell bodies (PMID:33199649, PMID:34939924). Its repressive activity is dynamically tuned by post-translational modification: CK2 phosphorylates S499 and IRE1 phosphorylates FMRP under ER stress, and phosphorylation reconfigures FMRP function—releasing the sequestered m6A reader YTHDF1 to permit activity-dependent translation (PMID:27957526, PMID:35191199, PMID:37949069). FMRP reads m6A-modified mRNA to drive CRM1-dependent nuclear export during neural differentiation (PMID:31340148), undergoes mGluR-stimulated SUMOylation that controls its homomerization within dendritic granules to regulate spine pruning (PMID:29472612), and engages in phosphorylation-dependent liquid-liquid phase separation with CAPRIN1 that tunes deadenylation and translation rates (PMID:31439799). FMRP integrates into miRNA and translational-repression machinery through interactions with MOV10 and AGO2, links to the Rac1/actin pathway by repressing PP2Acβ mRNA translation, and supports local translation of the mitochondrial fission factor MFF at mitochondrial fission sites within ribosome-rich granules (PMID:15703194, PMID:25464849, PMID:39548330, PMID:31291981).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Established that FMRP is an RNA-binding protein with defined RNA-binding domains and broad mRNA target range, framing it as a regulator of mRNA metabolism rather than a structural protein.

    Evidence In vitro filter-binding and stoichiometric analysis identifying two KH/RNP domains and Kd measurement of self-mRNA binding

    PMID:7692601

    Open questions at the time
    • Did not identify the cellular consequence of binding
    • No sequence/structure specificity defined for the bulk of targets
  2. 1997 High

    Localized FMRP to ribosomes and the cytoplasm of neurons, with a minority nuclear pool, establishing a ribosome-associated function and nucleocytoplasmic shuttling.

    Evidence Immunoelectron microscopy and subcellular fractionation in mouse brain and testis showing co-sedimentation with the 60S subunit

    PMID:9259278

    Open questions at the time
    • Did not distinguish active vs. stalled ribosome association
    • Functional role of the nuclear pool not defined
  3. 2003 High

    Defined the structural basis of RGG-box recognition of RNA G-quartets and linked G-quartet/RNA dimerization to RNP particle assembly, explaining target selectivity beyond the KH domains.

    Evidence NMR structural characterization of FMRP RGG box–RNA complexes across multiple targets

    PMID:13130134

    Open questions at the time
    • In vivo relevance of RNA:RNA dimerization not established
    • Did not connect G-quartet binding to translational outcome
  4. 2003 High

    Connected FMRP polyribosome association to in vivo cargo regulation, showing that FMRP loss alters abundance and distribution of bound mRNAs and their proteins.

    Evidence APRA, UV-crosslinking, filter binding, and Fmr1 KO mouse analysis

    PMID:12575950

    Open questions at the time
    • Did not resolve whether regulation is repression vs. stabilization
    • Mechanism of translational control unresolved
  5. 2005 Medium

    Separated the domain requirements for FMRP function, showing KH domains drive polyribosome association while the RGG box mediates other aspects such as localization.

    Evidence Domain deletion/point-mutation constructs with polyribosome fractionation in neuroblastoma cells

    PMID:16098133

    Open questions at the time
    • Single cell type and overexpression context
    • Did not map RGG-dependent localization mechanistically
  6. 2005 High

    Linked FMRP to cytoskeletal signaling by identifying PP2Acβ mRNA as a translationally repressed target downstream of Rac1-actin remodeling.

    Evidence Fmr1 KO fibroblasts, KH1/KH2 point mutants, actin-remodeling assays, UV-crosslinking and pulldown of pp2acbeta 5'-UTR

    PMID:15703194

    Open questions at the time
    • Studied in fibroblasts rather than neurons
    • Direct connection to spine actin dynamics not established here
  7. 2007 High

    Placed FMRP within P-body and miRNA/NMD machinery, establishing it as a component of Argonaute-dependent translational repression complexes.

    Evidence Immunofluorescence colocalization and genetic epistasis with argonaute in Drosophila eye imaginal discs

    PMID:17178403

    Open questions at the time
    • Mammalian conservation of specific interactions not tested here
    • Did not identify direct mRNA targets in this pathway
  8. 2011 High

    Defined the core repressive mechanism: FMRP binds coding regions of synaptic/autism-linked mRNAs and reversibly stalls ribosomes, giving a transcriptome-wide target map.

    Evidence HITS-CLIP plus brain polyribosome-programmed in vitro translation

    PMID:21784246

    Open questions at the time
    • Stalling mechanism at codon level not resolved
    • Did not address mRNA stability effects
  9. 2014 High

    Resolved FMRP's dual role in miRNA silencing through MOV10, with the RGG box protecting some co-bound mRNAs from AGO2 while permitting silencing of others.

    Evidence Reciprocal Co-IP, iCLIP, and domain mapping of FMRP-MOV10 interaction

    PMID:25464849 PMID:31740951

    Open questions at the time
    • Determinants of which mRNAs are protected vs. silenced unclear
    • Did not link to specific synaptic phenotypes
  10. 2016 High

    Identified post-translational and signaling control of FMRP, with CK2 phosphorylation at S499 and SUMOylation gating its activity and granule behavior.

    Evidence In vitro CK2 kinase assay with phospho-site mutagenesis; biochemical SUMO reconstitution with FRAP and molecular replacement in neurons

    PMID:27957526 PMID:29472612

    Open questions at the time
    • Full phospho-code and its targets incompletely mapped
    • Kinetics linking modification to specific mRNA derepression not fully defined
  11. 2016 High

    Connected FMRP to defined synaptic and miRNA-biogenesis effectors, repressing Dgkκ-dependent plasticity and promoting Drosha translation.

    Evidence CLIP, Fmr1 KO, knockdown and overexpression rescue (Dgkκ); RIP, polysome analysis and KO mouse (Drosha)

    PMID:26993298 PMID:27233938

    Open questions at the time
    • Direction of translational effect differs by target without unifying rule
    • In vivo Drosha-pathway consequences not fully traced
  12. 2019 High

    Showed FMRP regulates RNA fate through phase separation and m6A reading, coupling condensate biophysics to deadenylation/translation and to CRM1-dependent nuclear export.

    Evidence NMR and in vitro phase separation/deadenylation assays with CAPRIN1; m6A-seq, Fmr1/Mettl14 KO, CRM1 inhibition and export-deficient rescue

    PMID:31340148 PMID:31439799

    Open questions at the time
    • In vivo extent of condensate-driven regulation unquantified
    • Coordination of nuclear m6A reading with cytoplasmic repression unclear
  13. 2019 Medium

    Established FMRP as a node in activity-dependent synaptic translation via an inhibitory FMRP-MOV10-AGO2 complex released by NMDAR stimulation.

    Evidence Co-IP of ternary complex and NMDAR-stimulation translation reporters in rat synaptoneurosomes

    PMID:31291981

    Open questions at the time
    • Phosphorylation switch inferred rather than directly mapped
    • Single-lab synaptoneurosome system
  14. 2020 High

    Refined the genome-wide regulatory logic, showing FMRP stabilizes optimal-codon transcripts and acts cell-type-specifically across human neural lineages and glia.

    Evidence Ribosome profiling, metabolic labeling, codon-optimality analysis in mouse cortex; CLIP-seq/RNA-seq in human iPSC neural cells; conditional astroglial KO with miR-128-3p rescue

    PMID:32179589 PMID:32958647 PMID:33199649

    Open questions at the time
    • Mechanism linking codon optimality to FMRP binding incomplete
    • Cell-type-specific target rules not unified
  15. 2021 High

    Demonstrated compartment-specific FMRP function—dendritic repression versus somatic stabilization—and implicated FMRP sequestration in FUS-ALS pathology.

    Evidence Compartment-specific CLIP+TRAP in CA1-specific KO mice; FUS-ALS iPSC/mouse models with co-phase separation and HuD-binding competition assays

    PMID:34290090 PMID:34471224 PMID:34939924

    Open questions at the time
    • What determines repression vs. stabilization at a given site unresolved
    • FUS-FMRP interplay characterized in single labs
  16. 2022 High

    Extended FMRP function beyond neurons to peripheral disease and revealed PABP-dependent mRNA stabilization, including roles in atherosclerosis and antitumor immunity.

    Evidence RIP-seq, SILAC proteomics, and FMRP-PABPC Co-IP in human neurons; IRE1-driven phospho-regulation in macrophages; FMRP KO tumor/immune models

    PMID:35191199 PMID:36356584 PMID:36395212

    Open questions at the time
    • Generality of stabilization vs. repression across tissues unclear
    • Disease relevance of immune/cholesterol functions in humans not established
  17. 2023 High

    Connected FMRP phosphorylation to a concrete activity-dependent switch by showing it releases YTHDF1 to enable translation, and identified a species-specific CNOT1/RACK1 axis.

    Evidence Co-IP, phosphomimetic mutants, FXS organoid and YTHDF1-inhibitor rescue (YTHDF1); multiomics, Co-IP, RACK1 knockdown and electrophysiology in human neurons (CNOT1)

    PMID:37820724 PMID:37949069

    Open questions at the time
    • Endogenous kinase(s) driving the YTHDF1 switch not fully defined
    • Species specificity of RACK1 regulation mechanistically unexplained
  18. 2024 High

    Revealed a spatially targeted role for FMRP in organelle biology, promoting local MFF translation at mitochondrial fission sites within ribosome-rich granules.

    Evidence Cryo-electron tomography, real-time translation imaging, and Rab7 GTP-hydrolysis manipulation in neurons

    PMID:39548330

    Open questions at the time
    • How FMRP granules are recruited to fission midzones mechanistically unresolved
    • Relationship to repressive vs. promoting modes of FMRP unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what single set of molecular rules dictates whether FMRP represses, stalls, stabilizes, or promotes translation of a given target, and how phosphorylation, SUMOylation, condensate state, and m6A reading are integrated in vivo.
  • No unifying determinant of repression vs. stabilization per target
  • Integration of multiple post-translational modifications not modeled
  • Quantitative contribution of condensate biophysics in living neurons unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0045182 translation regulator activity 4 GO:0140313 molecular sequestering activity 3
Localization
GO:0005840 ribosome 4 GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3
Partners
AGO2CAPRIN1CNOT1FXR1FXR2MOV10PABPC1YTHDF1
Complex memberships
FMRP-MOV10-AGO2 repressive complexpolyribosomal mRNP

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 FMRP contains two RNP/KH domains that mediate RNA binding in stoichiometric ratios (two RNA binding sites per molecule), and binds its own mRNA with high affinity (Kd = 5.7 nM) as well as ~4% of human fetal brain mRNAs. In vitro RNA binding assays (filter binding, stoichiometric analysis), domain identification Science High 7692601
2003 FMRP RGG box specifically recognizes RNA G-quartet structures; this interaction shows heterogeneous binding modes across RNA targets and G-quartet formation can be mediated by RNA dimerization, suggesting a role for RNA:RNA interactions in RNP particle assembly. NMR spectroscopy structural characterization of FMRP RGG box–RNA complexes RNA High 13130134
2003 FMRP is associated with polyribosomes as a cytoplasmic mRNP component; approximately 60% of APRA-identified FMRP RNA cargoes directly associate with FMRP by UV-crosslinking and filter binding. Loss of FMRP in Fmr1 knockout mice alters abundance and subcellular distribution of these cargo mRNAs and their encoded proteins. Antibody-positioned RNA amplification (APRA), UV-crosslinking, filter binding assays, Fmr1 KO mouse analysis Neuron High 12575950
1997 FMRP, FXR1P, and FXR2P are colocalized in the cytoplasm of neurons and co-sediment with the 60S ribosomal subunit; FMRP is found predominantly associated with ribosomes by immunoelectron microscopy, with a minority in the nucleus, consistent with nucleocytoplasmic shuttling. Immunohistochemistry, immunoelectron microscopy, subcellular fractionation in mouse brain and testis Human molecular genetics High 9259278
2000 FMRP, FXR1P, and FXR2P are associated with polyribosomes as cytoplasmic mRNP particles; immunoelectron microscopy on hippocampal neurons shows the majority of all three proteins in association with ribosomes, with a minority in the nucleus, indicating nucleocytoplasmic shuttling. Immunoelectron microscopy, Western blotting, immunolabeling in WT and Fmr1 KO mice Experimental cell research High 10912798
2004 FMRP isoform 18 and the RNA transport protein IMP1 co-localize on common mRNAs predominantly in cytoplasmic granular structures in living mammalian cells; they interact independently of RNA, and tethering FMRP to an mRNA recruits IMP1 to the same mRNA, causing granule formation. This links mRNA transport to translational repression. Live-cell imaging of RNA-protein interactions (bimolecular fluorescence complementation), Co-IP, granule formation assay The EMBO journal Medium 15282548
2005 FMRP interacts with the Rac1 pathway in murine fibroblasts: Rac1 activation induces relocalization of FMRP partners; loss of FMRP or KH1/KH2 domain point mutations alters Rac1-induced actin remodeling. FMRP loss reduces phospho-ADF/Cofilin and increases PP2Ac levels. FMRP binds the 5'-UTR of pp2acbeta mRNA with high affinity, acting as a negative regulator of its translation. Fmr1 KO fibroblasts, point-mutation constructs (KH1, KH2), actin remodeling assays, UV-crosslinking, immunoprecipitation, biochemical pulldown Human molecular genetics High 15703194
2006 FMRP-containing neuronal RNPs in Drosophila neurons contain P body components (Dcp1p, Xrn1p/Pacman, Dhh1p/Me31B, Argonaute) and components of miRNA, NMD, and translational repression pathways. Me31B participates with FMRP-associated Scd6p/trailer hitch in FMRP-driven, argonaute-dependent translational repression in developing eye imaginal discs. Immunofluorescence colocalization, genetic interaction assays in Drosophila, epistasis with argonaute Neuron High 17178403
2011 FMRP interacts with the coding region of polyribosomal mRNAs encoding pre- and postsynaptic proteins and autism-linked transcripts, and reversibly stalls ribosomes on its specific target mRNAs. This ribosome-stalling mechanism was demonstrated using a brain polyribosome-programmed translation system. HITS-CLIP (high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation), brain polyribosome-programmed in vitro translation system Cell High 21784246
2005 Point mutations in the KH1 or KH2 domains of FMRP abrogate its polyribosome association in transfected neuroblastoma cells, while deletion of the RGG box does not. This suggests KH domains are required for polyribosome association, whereas the RGG box may mediate other aspects of mRNA metabolism such as localization. Domain deletion/point mutation constructs expressed in neuroblastoma cells, polyribosome fractionation Genes, brain, and behavior Medium 16098133
2014 FMRP associates with MOV10 (RNA helicase) directly and in an RNA-dependent manner. FMRP facilitates MOV10 association with RNAs, and the FMRP RGG box protects a co-bound subset of mRNAs from AGO2 association, preventing microRNA-mediated silencing on those targets while allowing MOV10 to facilitate miRNA-mediated silencing of other RNAs. Co-IP (direct and RNA-dependent), RNA immunoprecipitation, iCLIP, domain mapping Cell reports High 25464849
2016 FMRP is mostly associated with Dgkκ (diacylglycerol kinase kappa) mRNA in cortical neurons (by CLIP); absence of FMRP abolishes mGluR-dependent DGK activity and reduces Dgkκ expression. Knockdown of Dgkκ phenocopies FXS spine/plasticity defects; overexpression of Dgkκ rescues dendritic spine defects in Fmr1 KO neurons. CLIP in cortical neurons, Fmr1 KO mouse, shRNA knockdown, overexpression rescue Proceedings of the National Academy of Sciences of the United States of America High 27233938
2016 Casein kinase II (CK2) phosphorylates FMRP at serine residue S499 in mammals. S499 phosphorylation by CK2 promotes secondary phosphorylation of nearby residues, which are modulated by mGluR-I and PP2A pathways. In vitro kinase assay with CK2 and FMRP, phospho-site mutagenesis, mGluR-I and PP2A pathway manipulation eNeuro Medium 27957526
2018 FMRP is a substrate of the SUMO pathway in neurons; sumoylation is promoted by mGluR activation and controls FMRP homomerization within dendritic mRNA granules, which in turn regulates dendritic spine elimination and maturation. Biochemical reconstitution of SUMOylation, molecular replacement strategy, live-cell imaging (FRAP), mGluR activation assays in neurons Nature communications High 29472612
2019 FMRP and CAPRIN1 undergo phosphorylation-dependent liquid-liquid phase separation; NMR spectroscopy reveals arginine-rich and aromatic-rich IDR interactions drive co-phase separation. Different FMRP serine/threonine and CAPRIN1 tyrosine phosphorylation patterns control phase separation propensity and RNA subcompartmentalization, and tune deadenylation and translation rates in vitro. NMR spectroscopy of FMRP-CAPRIN1 condensates, in vitro phase separation assays, in vitro deadenylation/translation assays, phosphomimetic mutants Science High 31439799
2019 FMRP reads m6A-modified mRNA and promotes nuclear export of methylated mRNA targets during neural differentiation via the CRM1 export pathway. Fmr1 KO phenocopies Mettl14 cKO in causing nuclear retention of m6A-modified mRNAs and delayed neural progenitor cell cycle progression. Nuclear export-deficient FMRP fails to rescue the nuclear retention defect. RNA-seq, m6A-seq, Fmr1 KO mouse, Mettl14 cKO mouse, m6A-RIP, CRM1 inhibition, rescue with WT vs. nuclear export-deficient FMRP Cell reports High 31340148
2015 Fmrp biochemically interacts with the Adar2a protein in zebrafish, and loss of fmr1 increases expression levels of adar genes and Adar2 protein, resulting in mildly increased A-to-I RNA editing levels at conserved neuronal synaptic Adar targets. Loss of Fmrp results in hyperlocomotor activity and increased axonal branching and synaptic density. Co-immunoprecipitation (Fmrp-Adar2a interaction), Western blotting, deep sequencing (multiplex PCR-based), live imaging of axons/synapses in fmr1-/- zebrafish PLoS genetics Medium 26637167
2020 FMRP preferentially binds mRNAs with optimal codons and stabilizes such transcripts through direct interactions via the translational machinery. In FMRP-deficient cortical neurons, down-regulated mRNAs are mostly responsible for neuronal/synaptic functions and their down-regulation is caused by elevated degradation correlated with codon optimality. Ribosome profiling, RNA sequencing, metabolic RNA labeling, codon optimality analysis in Fmr1 KO mouse cortex Proceedings of the National Academy of Sciences of the United States of America High 33199649
2020 FMRP CLIP targets in human neural cells preferentially include long transcripts; FMRP regulates both common and cell-type-specific gene sets across neural progenitors and neurons. Integrative network analysis defines critical pathways regulated by FMRP in human neurodevelopment. Modified CLIP-seq, RNA-seq in FMR1 KO human iPSC-derived neural cells (dorsal/ventral forebrain progenitors, excitatory/inhibitory neurons), integrative network analysis Genome research Medium 32179589
2021 FMRP differentially regulates translation of functionally distinct mRNA modules in CA1 dendrites vs. cell bodies: in dendrites FMRP targets ~15-20% of mRNAs encoding synaptic functions (acting as translational repressor — dendritic FMRP targets show increased ribosome association in Fmr1 KO), while in cell bodies FMRP targets involved in chromatin regulation are downregulated (FMRP stabilizes mRNAs with stalled ribosomes). Compartment-specific CLIP (neuropil microdissection) + TRAP in conditionally tagged mice, CA1-specific Fmr1 KO eLife High 34939924
2021 In FUS-ALS motor neurons, mutant FUS condensates sequester FMRP and promote its phase separation in axons, leading to repression of translation of FMRP-bound RNAs. FUS and FMRP copartition and repress translation in vitro. Mouse and human iPSC FUS-ALS models, condensate imaging, in vitro co-phase separation assay, translational reporter assays, ribosome profiling Science advances Medium 34290090
2022 FMRP represses antitumor immune responses in cancer cells by repressing CCL7 (chemoattractant) and upregulating immunomodulators IL-33, PROS1, and extracellular vesicles. FMRP-deficient tumors are infiltrated by activated T cells and show impaired tumor growth in mice. FMRP knockout in cancer cell lines, tumor growth in mice, T cell infiltration assays, protein quantification Science Medium 36395212
2022 ER stress-induced activation of IRE1 kinase leads to FMRP phosphorylation, which enhances FMRP's translation inhibition activity; this suppresses macrophage cholesterol efflux and efferocytosis. FMRP deficiency and pharmacological IRE1 kinase inhibition enhances cholesterol efflux and reduces atherosclerosis in mice. Proteomics (Baboo et al.), phospho-site identification by MS, IRE1 kinase inhibitor pharmacology, Fmr1 KO macrophage functional assays, in vivo atherosclerosis mouse model EMBO molecular medicine Medium 35191199
2023 FMRP phosphorylation by upstream neuronal stimulation releases YTHDF1 from FMRP sequestration; unphosphorylated FMRP sequesters YTHDF1 away from ribosomes, suppressing translation of YTHDF1 targets, whereas phosphorylation of FMRP releases YTHDF1 to condense with ribosomal proteins and promote translation. This mechanism mediates activity-dependent neuronal translation. Co-IP (FMRP-YTHDF1 interaction), phosphomimetic/phosphodeficient FMRP mutants, neuronal stimulation assays, FXS organoid model, small molecule YTHDF1 inhibitor rescue Molecular cell High 37949069
2022 FMRP footprints (by RIP-seq) are densest in 5' UTRs and target GC-rich, structured sequences independent of protein-coding potential. FMRP directly binds cytoplasmic poly(A)-binding protein and protects mRNAs from deadenylation, sequesters polyadenylated mRNAs into stabilized and translationally repressed complexes. FMRP loss generally results in mRNA destabilization and increased protein production per FMRP target. RIP-seq, SILAC-LC-MS/MS proteomics, integrative transcriptomics, co-IP (FMRP–PABPC), in human neuronal cells Molecular cell High 36356584
2024 FMRP granules are recruited to mitochondrial midzones in axons and dendrites, marking mitochondrial fission sites. Endolysosomal vesicles (via Rab7 GTP hydrolysis) contribute to FMRP granule positioning around mitochondria. Cryo-electron tomography reveals mitochondria-associated FMRP granules are ribosome-rich. Real-time translation imaging demonstrates FMRP promotes local translation of mitochondrial fission factor (MFF) at mitochondrial midzones, selectively enabling replicative fission. Disrupting FMRP dysregulates MFF translation and perturbs fission dynamics. Cryo-electron tomography, real-time translation imaging, live-cell imaging (mitochondrial fission dynamics), Rab7 GTP hydrolysis manipulation, FMRP loss-of-function in neurons Nature cell biology High 39548330
2023 FMRP interacts with CNOT1 to maintain levels of RACK1 protein in human neurons, representing a species-specific regulatory interaction. FMRP-deficient neurons exhibit mitochondrial dysfunction and hyperexcitability; genetic reduction of RACK1 phenocopies these deficits. Multiomics (FMRP CLIP-seq + proteomics) in human iPSC-derived neurons, Co-IP (FMRP-CNOT1), RACK1 knockdown, mitochondrial function assays, electrophysiology, human fetal cortical slice experiments Neuron High 37820724
2020 FMRP regulates centrocortin (cen) mRNA localization to centrosomes in Drosophila embryos; loss of FMRP function mislocalizes cen mRNA, alters cognate protein localization to centrosomes, and impairs spindle morphogenesis and genome stability. Drosophila genetics (FMRP loss-of-function), live imaging of mRNA localization, centrosome assays, mitotic spindle analysis The Journal of cell biology Medium 33196763
2016 The FMRP RGG box protects a subset of co-bound mRNAs (with MOV10) from AGO2 association; N-terminus of MOV10 is required for this protection and for FMRP RGG box-dependent binding to the SC1 RNA G-Quadruplex and for neurite outgrowth. FMRP has a global role in miRNA-mediated translational regulation by recruiting AGO2 to a large subset of RNAs in mouse brain. Domain mapping (FMRP, MOV10, AGO2), CLIP-seq in mouse brain, neurite outgrowth assay, RNA immunoprecipitation Nucleic acids research Medium 31740951
2016 FMRP promotes translation of Drosha mRNA: FMRP binds Drosha mRNA and enhances its translation (shown by immunoprecipitation and polysome analysis). Loss of FMRP in Fmr1 KO mice reduces DROSHA protein (but not mRNA), leading to accumulation of pri-miRNAs and reduction of corresponding pre-miRNAs and mature miRNAs. RNA immunoprecipitation, polysome analysis, Fmr1 KO mouse (hippocampus), FMRP overexpression/knockdown in Neuro-2a cells Molecular neurobiology Medium 26993298
2021 In FUS-ALS motor neurons, mutant FUS leads to upregulation of HuD protein through competition with FMRP for HuD mRNA 3'UTR binding; FMRP normally suppresses HuD mRNA translation by binding its 3'UTR, and displacement of FMRP by mutant FUS increases HuD levels and stabilizes NRN1 and GAP43 transcripts. Human iPSC and mouse FUS-ALS models, RNA binding competition assay (FMRP vs FUS for HuD 3'UTR), Western blotting, RNA stability assays Communications biology Medium 34471224
2020 Selective loss of astroglial FMRP cell-autonomously up-regulates miR-128-3p in astroglia, suppressing developmental expression of astroglial mGluR5. In vivo inhibition of miR-128-3p in FMRP-deficient astroglia rescues decreased mGluR5 function. FMRP preferentially regulates protein expression through posttranscriptional mechanisms in astroglia. Conditional Fmr1 KO in astroglia, miRNA measurement, in vivo miR-128-3p inhibitor, mGluR5 functional assays, transcriptome and proteome profiling Proceedings of the National Academy of Sciences of the United States of America High 32958647
2019 FMRP is required for NMDAR-stimulated translation at synapses. In rat cortical synaptoneurosomes, FMRP, MOV10, and AGO2 form an inhibitory complex on a subset of NMDAR-responsive mRNAs; upon NMDAR stimulation MOV10 dissociates from AGO2 promoting translation of target mRNAs. FMRP phosphorylation appears to be the switch for NMDAR-mediated translation. Rat cortical synaptoneurosome preparation, Co-IP of FMRP-MOV10-AGO2 complex, NMDAR stimulation assays, phosphorylation state analysis, translation reporter assays Molecular brain Medium 31291981

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 1678 21784246
1993 FMR1 protein: conserved RNP family domains and selective RNA binding. Science (New York, N.Y.) 626 7692601
2003 RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 409 12575950
2018 Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene. Cell 377 29456084
2013 The translation of translational control by FMRP: therapeutic targets for FXS. Nature neuroscience 373 23584741
2021 The molecular biology of FMRP: new insights into fragile X syndrome. Nature reviews. Neuroscience 295 33608673
2006 Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P bodies. Neuron 288 17178403
2006 The FMR1 premutation and reproduction. Fertility and sterility 286 17074338
2019 Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation. Science (New York, N.Y.) 275 31439799
2004 Phenotypic variation and FMRP levels in fragile X. Mental retardation and developmental disabilities research reviews 233 14994286
2019 FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export. Cell reports 227 31340148
2014 Modeling fragile X syndrome in the Fmr1 knockout mouse. Intractable & rare diseases research 196 25606362
1997 Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. Human molecular genetics 163 9259278
2004 Visualization of RNA-protein interactions in living cells: FMRP and IMP1 interact on mRNAs. The EMBO journal 152 15282548
2000 Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse. Experimental cell research 148 10912798
2011 CGG repeat in the FMR1 gene: size matters. Clinical genetics 145 21651511
2005 FMRP interferes with the Rac1 pathway and controls actin cytoskeleton dynamics in murine fibroblasts. Human molecular genetics 124 15703194
2011 Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 120 21482951
1995 Contribution of the FMR1 gene mutation to human intellectual dysfunction. Nature genetics 120 7581460
2014 Associated features in females with an FMR1 premutation. Journal of neurodevelopmental disorders 115 25097672
2006 mRNPs, polysomes or granules: FMRP in neuronal protein synthesis. Current opinion in neurobiology 111 16707258
2003 G-quartet-dependent recognition between the FMRP RGG box and RNA. RNA (New York, N.Y.) 107 13130134
2009 FMR1: a gene with three faces. Biochimica et biophysica acta 100 19233246
2003 Sunrise at the synapse: the FMRP mRNP shaping the synaptic interface. Neuron 98 12597853
2005 FMRP RNA targets: identification and validation. Genes, brain, and behavior 95 16098133
2014 MOV10 and FMRP regulate AGO2 association with microRNA recognition elements. Cell reports 94 25464849
2010 Abnormal mGlu 5 receptor/endocannabinoid coupling in mice lacking FMRP and BC1 RNA. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 94 20393458
2010 The behavioral phenotype of FMR1 mutations. American journal of medical genetics. Part C, Seminars in medical genetics 91 20981777
2002 Timing of the absence of FMR1 expression in full mutation chorionic villi. Human genetics 88 12107447
2018 Aberrant RNA translation in fragile X syndrome: From FMRP mechanisms to emerging therapeutic strategies. Brain research 86 29653083
2017 Fragile X syndrome: An overview and update of the FMR1 gene. Clinical genetics 86 28617938
2013 The FMRP regulon: from targets to disease convergence. Frontiers in neuroscience 85 24167470
2022 Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion. Science (New York, N.Y.) 84 36395212
2016 Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons. Proceedings of the National Academy of Sciences of the United States of America 76 27233938
2014 The cognitive neuropsychological phenotype of carriers of the FMR1 premutation. Journal of neurodevelopmental disorders 72 25136377
2023 FMRP phosphorylation modulates neuronal translation through YTHDF1. Molecular cell 71 37949069
2015 Fmrp Interacts with Adar and Regulates RNA Editing, Synaptic Density and Locomotor Activity in Zebrafish. PLoS genetics 69 26637167
2017 Rare FMR1 gene mutations causing fragile X syndrome: A review. American journal of medical genetics. Part A 68 29178241
2011 FMR1 premutation and full mutation molecular mechanisms related to autism. Journal of neurodevelopmental disorders 68 21617890
1996 FMR1 in global populations. American journal of human genetics 65 8644711
2010 The role of G-quadruplex in RNA metabolism: involvement of FMRP and FMR2P. Biochimie 63 20570707
2014 CNS expression of murine fragile X protein (FMRP) as a function of CGG-repeat size. Human molecular genetics 58 24463622
2018 Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation. Nature communications 55 29472612
2014 SnapShot: FMRP mRNA targets and diseases. Cell 54 25215498
2009 Examination of FMR1 transcript and protein levels among 74 premutation carriers. Journal of human genetics 54 19927162
2000 Premature ovarian failure and the FMR1 gene. Seminars in reproductive medicine 54 11299521
2020 FMRP links optimal codons to mRNA stability in neurons. Proceedings of the National Academy of Sciences of the United States of America 53 33199649
2019 Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions. PloS one 52 31891607
2005 Parkinsonism, FXTAS, and FMR1 premutations. Movement disorders : official journal of the Movement Disorder Society 52 15390127
2005 SCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast. The EMBO journal 52 15660136
2020 Identification of FMR1-regulated molecular networks in human neurodevelopment. Genome research 50 32179589
2003 Expression of the FMR1 gene. Cytogenetic and genome research 49 14526172
2021 FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation. Science advances 48 34290090
2021 FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons. eLife 48 34939924
2000 FMR1 gene and fragile X syndrome. American journal of medical genetics 48 11180223
2000 Mapping of the POF1 locus and identification of putative genes for premature ovarian failure. Molecular human reproduction 47 10729312
2023 Antisense oligonucleotide rescue of CGG expansion-dependent FMR1 mis-splicing in fragile X syndrome restores FMRP. Proceedings of the National Academy of Sciences of the United States of America 46 37364131
2012 Unstable mutations in the FMR1 gene and the phenotypes. Advances in experimental medicine and biology 46 23560306
2015 Fragile X mental retardation protein (FMRP) interacting proteins exhibit different expression patterns during development. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 45 25681562
2016 Identification of consensus binding sites clarifies FMRP binding determinants. Nucleic acids research 44 27378784
1999 Expression of FMR1, FXR1, and FXR2 genes in human prenatal tissues. Journal of neuropathology and experimental neurology 43 10446811
2020 Regulation of RNA granules by FMRP and implications for neurological diseases. Traffic (Copenhagen, Denmark) 42 32374065
2019 The translational regulator FMRP controls lipid and glucose metabolism in mice and humans. Molecular metabolism 42 30686771
2020 Novel FMRP interaction networks linked to cellular stress. The FEBS journal 40 32525608
2013 From FMRP function to potential therapies for fragile X syndrome. Neurochemical research 39 24346713
2021 FMR1 and Autism, an Intriguing Connection Revisited. Genes 35 34440392
2014 Chromosome fragility and the abnormal replication of the FMR1 locus in fragile X syndrome. Human molecular genetics 35 24419320
2010 The developmental roles of FMRP. Biochemical Society transactions 35 20298211
2003 The RNA binding protein FMRP: new connections and missing links. Biology of the cell 34 12867085
2014 SnapShot: FMRP interacting proteins. Cell 33 25259928
2010 The FMR1 gene as regulator of ovarian recruitment and ovarian reserve. Obstetrical & gynecological survey 33 20955631
2016 Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP. eNeuro 31 27957526
2022 Intercepting IRE1 kinase-FMRP signaling prevents atherosclerosis progression. EMBO molecular medicine 30 35191199
2021 ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity. Communications biology 30 34471224
2017 Gene-set analysis shows association between FMRP targets and autism spectrum disorder. European journal of human genetics : EJHG 30 28422133
2024 FMRP regulates MFF translation to locally direct mitochondrial fission in neurons. Nature cell biology 29 39548330
2023 Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development. Neuron 29 37820724
2020 centrocortin RNA localization to centrosomes is regulated by FMRP and facilitates error-free mitosis. The Journal of cell biology 28 33196763
2021 Altered inflammatory response in FMRP-deficient microglia. iScience 27 34820601
2022 FMRP modulates the Wnt signalling pathway in glioblastoma. Cell death & disease 26 35982038
2016 Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene. Genes 26 27983607
2020 The FMRP-MOV10 complex: a translational regulatory switch modulated by G-Quadruplexes. Nucleic acids research 25 31740951
2020 FMRP and CYFIP1 at the Synapse and Their Role in Psychiatric Vulnerability. Complex psychiatry 25 34883502
2014 YCL047C/POF1 is a novel nicotinamide mononucleotide adenylyltransferase (NMNAT) in Saccharomyces cerevisiae. The Journal of biological chemistry 25 24759102
2007 Differential expression of Fmr-1 mRNA and FMRP in female mice brain during aging. Molecular biology reports 25 17899445
2022 Mechanisms of the FMR1 Repeat Instability: How Does the CGG Sequence Expand? International journal of molecular sciences 24 35628235
2005 Characterisation of Fmrp in zebrafish: evolutionary dynamics of the fmr1 gene. Development genes and evolution 24 15818485
2021 Emergence of Developmental Delay in Infants and Toddlers With an FMR1 Mutation. Pediatrics 23 33911031
2017 Altered expression of the FMR1 splicing variants landscape in premutation carriers. Biochimica et biophysica acta. Gene regulatory mechanisms 23 28888471
2020 Elevated FMR1-mRNA and lowered FMRP - A double-hit mechanism for psychiatric features in men with FMR1 premutations. Translational psychiatry 22 32576818
2020 Genetic association of FMRP targets with psychiatric disorders. Molecular psychiatry 22 33077856
2022 Integrative omics indicate FMRP sequesters mRNA from translation and deadenylation in human neuronal cells. Molecular cell 21 36356584
2020 Astroglial FMRP deficiency cell-autonomously up-regulates miR-128 and disrupts developmental astroglial mGluR5 signaling. Proceedings of the National Academy of Sciences of the United States of America 21 32958647
2016 RNA Secondary Structure Modulates FMRP's Bi-Functional Role in the MicroRNA Pathway. International journal of molecular sciences 21 27338369
2018 Reevaluation of FMR1 Hypermethylation Timing in Fragile X Syndrome. Frontiers in molecular neuroscience 19 29467618
2018 Handling FMRP and its molecular partners: Structural insights into Fragile X Syndrome. Progress in biophysics and molecular biology 19 30905341
2016 Involvement of FMRP in Primary MicroRNA Processing via Enhancing Drosha Translation. Molecular neurobiology 19 26993298
2020 Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP. Molecular autism 18 33054857
2019 NMDAR mediated translation at the synapse is regulated by MOV10 and FMRP. Molecular brain 18 31291981
2017 Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 18 28719003

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