| 1995 |
FXR1 protein contains two KH domains and an RGG box, binds RNA in vitro, and localizes to the cytoplasm; it forms heteromers with FMR1 and FXR2 both in vivo and in vitro, demonstrating that these three proteins interact as a family complex. |
Co-immunoprecipitation, in vitro RNA binding assay, subcellular fractionation/immunofluorescence |
The EMBO journal |
High |
7489725 7781595
|
| 1997 |
FXR1 protein co-sediments with the 60S ribosomal subunit in cell fractionation experiments, consistent with a role in translational regulation. |
Sucrose gradient sedimentation / subcellular fractionation |
Human molecular genetics |
Medium |
9259278
|
| 2004 |
Fxr1 knockout mice die shortly after birth with disrupted skeletal and cardiac muscle architecture; in wild-type neonates Fxr1p localizes to costameric regions of muscle, and its absence causes delocalization of costameric proteins vinculin, dystrophin, and alpha-actinin, establishing FXR1 as essential for striated muscle integrity. |
Knockout mouse model, histochemistry, immunofluorescence localization |
Human molecular genetics |
High |
15128702
|
| 2007 |
FXR1 and AGO2 associate with the TNFα AU-rich element (ARE) exclusively during translation activation conditions (serum starvation); tethering and shRNA knockdown experiments demonstrate that both FXR1 and AGO2 are required for ARE-mediated translational upregulation of TNFα, and they are interdependent for this function. |
In vivo crosslinking-coupled affinity purification, tethering assay, shRNA knockdown, reporter assay |
Cell |
High |
17382880
|
| 2010 |
PAK1 directly binds the KH2 domain of FXR1 via an 11-residue segment in PAK1's autoinhibitory domain; active PAK1 phosphorylates FXR1 at Ser420; the familial FMR1(I304N) mutation equivalent in FXR1 abolishes PAK1 binding; Ser420 phosphorylation is required for FXR1 function during zebrafish muscle development. |
Co-immunoprecipitation, in vitro kinase assay, phospho-specific antibodies, site-directed mutagenesis, zebrafish rescue experiments |
Molecular cell |
High |
20417602
|
| 2010 |
X-ray crystal structures of the N-terminal tandem Tudor domains of FXR1 and FXR2 determined at 2.50 and 1.92 Å; these domains preferentially recognize trimethylated peptides in a sequence-specific manner, analogous to the tandem Tudor architecture of UHRF1. |
X-ray crystallography, biochemical peptide-binding assays |
PloS one |
High |
21072162
|
| 2010 |
FXR1 loss-of-function in Xenopus laevis causes abnormal eye development and cranial neural crest cartilage defects; genetic interaction experiments link FXR1 function to the miRNA-induced silencing complex (RISC) pathway, including Dicer, during anterior neural development. |
Morpholino knockdown in Xenopus, epistasis with Dicer and specific miRNAs |
Developmental biology |
Medium |
20197067
|
| 2013 |
Fbxo4 (SCF E3 ligase) directly ubiquitinates and degrades FXR1; purification of SCFFbxo4 complexes identified all three FXR family members as binding partners; FXR1 overexpression in turn attenuates Fbxo4 translation, creating a feedback loop that contributes to FXR1 overexpression in cancer. |
Affinity purification of SCFFbxo4, co-IP, in vivo ubiquitination assay, Fbxo4 knockout cell/tissue analysis |
Nature communications |
High |
29142209
|
| 2014 |
Cytoplasmic plakophilins 1 and 3 (PKP1/3) bind FXR1 in an RNA-independent manner; this interaction is part of mRNP complexes that stabilize desmoplakin and PKP2 mRNAs, and both PKP3 and FXR1 are required for PKP2 mRNA stability. |
Co-immunoprecipitation (RNase-sensitive and -insensitive), gain/loss-of-function mRNA stability assays |
Molecular and cellular biology |
Medium |
25225333
|
| 2016 |
FXR1 binds the G-quadruplex (G4) RNA structure in the 3′-UTR of p21 (CDKN1A) mRNA and promotes its degradation, thereby suppressing p21 protein expression; FXR1 also binds and stabilizes TERC RNA to maintain telomerase activity and bypass p53-mediated cellular senescence in oral squamous cell carcinoma. |
RNA immunoprecipitation, RNA pulldown, mRNA stability assay, shRNA knockdown, luciferase reporter, G4 structure analysis |
PLoS genetics |
Medium |
27606879
|
| 2017 |
FXR1 associates with intercalated disc proteins and directly binds Cx43, Cx45, and ZO-1 mRNAs as identified by BioID proximity assay and RNA immunoprecipitation; FXR1 stabilizes these mRNAs and promotes their translation; cardiac-specific overexpression of FXR1 in mice redistributes gap junctions and induces ventricular tachycardia. |
BioID proximity assay, RNA immunoprecipitation, mRNA stability assay, luciferase reporter, cardiac-specific FXR1 knockout and AAV-overexpression mice |
Circulation |
High |
29101288
|
| 2017 |
FXR1 recruits transcription factors STAT1 or STAT3 to gene promoters at the chromatin interface and regulates transcription; inhibition of FXR1 selectively blocks proliferation in cancer cells with homozygous deletion of both TP53 and FXR2 (collateral lethality). |
ChIP, chromatin association assays, siRNA knockdown, cell proliferation assays in TP53/FXR2 co-deleted cancer lines |
eLife |
Medium |
28767039
|
| 2018 |
FXR1 is identified as an HuR-interacting protein in vascular smooth muscle cells (interaction is RNA-tethered, abrogated by RNase); FXR1 binds the ARE and 3′-UTR element of TNFα mRNA (RNA EMSA, RIP) and destabilizes pro-inflammatory mRNAs; FXR1 is induced by the anti-inflammatory cytokine IL-19 and is required for IL-19-mediated reduction of HuR and TNFα. |
LC-MS/MS interactome, RNA EMSA, RIP, siRNA knockdown and overexpression, mRNA stability assay |
Cell reports |
High |
30067974
|
| 2019 |
Recessive loss-of-function mutations specifically in exon-15 of FXR1 (expressed only in cardiac and skeletal muscle isoforms) cause congenital multi-minicore myopathy in humans and mice; whole-body Fxr1 isoform depletion (Myf5-Cre) is neonatal lethal, whereas exon-15-specific mutations cause non-lethal myopathy. |
Whole-exome sequencing of patients, conditional mouse knockout models, histopathology |
Nature communications |
High |
30770808
|
| 2019 |
FXR1 negatively regulates FBXO4 mRNA via direct association with its 3′-UTR, promoting mRNA degradation in prostate cancer cells; FBXO4 knockdown rescues the tumor-suppressive phenotype of FXR1-deficient cells. |
RNA immunoprecipitation, RNA pulldown, luciferase reporter, siRNA knockdown, epistasis rescue experiments |
Functional & integrative genomics |
Medium |
30746571
|
| 2020 |
FXR1 controls stability of mature miR301a-3p in oral cancer cells; exoribonuclease PNPT1 degrades miR301a-3p when FXR1 is absent, and this degradation is blocked when FXR1-miRNA complex forms; FXR1 and miR301a-3p cooperatively target the 3′-UTR of p21 mRNA to promote its degradation. |
Small RNAseq, RNA stability assay, PNPT1 knockdown rescue, in vitro PNPT1 degradation assay, RIP |
PLoS genetics |
Medium |
31940341
|
| 2020 |
FXR1 alternative splicing in its intrinsically disordered serine/arginine-rich domain produces isoforms with distinct capacities to form RNA-dependent biomolecular condensates in cells and in vitro; tissue-specific splicing of fxr1 is required for Xenopus development, and mis-splicing disrupts muscle condensate formation. |
RT-PCR isoform characterization, Xenopus loss-of-function with splice-specific morpholinos, in vitro condensate assays, cell-based condensate imaging |
The Journal of cell biology |
High |
32328638
|
| 2020 |
Fxr1 is downregulated during synaptic scaling and sleep deprivation via a GSK3β-dependent mechanism; preventing Fxr1 downregulation during sleep deprivation blocks homeostatic modulation of surface AMPA receptors and synaptic strength; translatomic sequencing revealed Fxr1 contributes to sleep-deprivation-induced changes in neuronal translatomes. |
CRISPR/Cas9 somatic KO, gene overexpression, surface AMPA receptor assays, EEG recording, ribosome profiling/translatomics |
The EMBO journal |
High |
32893934
|
| 2021 |
FXR1 deletion from parvalbumin interneurons (PVIs) of the medial prefrontal cortex reduces PVI excitability, impairs gamma oscillations, and causes schizophrenia-like behaviors; FXR1 regulates expression of the T-type calcium channel Cacna1h/Cav3.2 in PVIs; Cav3.2 inhibition phenocopies and Cav3.2 elevation rescues FXR1 deficiency behavioral deficits. |
PVI-specific Fxr1 conditional KO, translational profiling (TRAP), electrophysiology, AAV-mediated rescue, behavioral testing |
Molecular psychiatry |
High |
33863995
|
| 2021 |
FXR1 binds AU-rich elements in the 3′-UTR of cMYC mRNA and stabilizes it; the RGG domain of FXR1 interacts with eIF4A1 and eIF4E; these dual interactions promote circularization of cMYC mRNA and recruitment of eukaryotic translation initiation factors to the translation start site, enhancing cMYC translation in ovarian cancer cells. |
RNA immunoprecipitation, co-immunoprecipitation, RPPA proteomics (SUnSET translation assay), mRNA stability assay, 5′-cap pulldown |
Cell reports |
Medium |
34731628
|
| 2022 |
FXR1 undergoes liquid-liquid phase separation (LLPS) in late spermatids to merge mRNP granules with the translation machinery, converting stored mRNAs to a translationally active state; germline-specific Fxr1 ablation impairs target mRNA translation and causes male infertility; a phase-separation-deficient FXR1(L351P) knock-in produces the same developmental defect. |
Germline-specific conditional KO mice, FXR1-L351P knock-in mice, LLPS assays, ribosome profiling, immunofluorescence |
Science |
High |
35951695
|
| 2022 |
FXR1 serves as a scaffold that recruits CFIm25 and CFIm68 to form a 3′-processing complex for sequence-specific poly(A) site recognition; FXR1 binding to TRAF1 mRNA leads to its nuclear stabilization and promotes cell proliferation in urothelial carcinoma. |
Co-immunoprecipitation, RNA immunoprecipitation, mass spectrometry, mRNA stability assay, knockdown functional assays |
Cell death & disease |
Medium |
35194031
|
| 2023 |
FXR1 binds cytoskeletal mRNAs (identified by RIP-seq) and stabilizes them; FXR1 also directly binds actin and interacts with cytoskeletal proteins Arp2 and CYFIP1 (a WAVE regulatory complex protein); FXR1 depletion decreases adhesion, migration, contraction, and GTPase activation in VSMCs; conditional FXR1-SMC knockout mice show decreased blood pressure. |
RIP-seq, mass spectrometry, actin binding assay, siRNA knockdown functional assays, telemetry blood pressure measurement in conditional KO mice |
Cell reports |
High |
37043351
|
| 2023 |
FXR1 interacts with MRE11 in the cytoplasm (partially at mitochondria); FXR1 depletion reduces oxidative stress responses and sensitizes cells to mitochondrial ROS inducer pyocyanin; FXR1 depletion also perturbs chromatin association of homologous recombination repair factors and sensitizes cells to camptothecin. |
Mass spectrometry identification of MRE11-binding partners, co-immunoprecipitation, subcellular fractionation, siRNA knockdown, cell viability assays |
Journal of radiation research |
Medium |
32211858
|
| 2023 |
ARL6IP1 mediates FXR1 interaction with the 5′-UTR of BACE1 mRNA to regulate BACE1 translation; conophylline treatment promotes ARL6IP1-FXR1 interaction and inhibits FXR1 binding to the BACE1 5′-UTR both in vitro and in vivo, reducing BACE1 protein levels. |
RNA pulldown combined with LC-MS/MS, co-immunoprecipitation, 5′-UTR luciferase reporter, in vivo mouse (APP/PS1) model |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
37216506
|
| 2024 |
PRMT5-mediated arginine methylation of FXR1 at R386, R388 (nuclear export signal) and R453, R455, R459 (RGG domain) is required for FXR1 binding to G-quadruplex (G4) RNA structures; PRMT5 loss-of-function inhibits FXR1 methylation and RNA-binding activity; eCLIP identifies G4-enriched mRNA targets including AHNAK, MAP1B, AHNAK2, HUWE1, DYNC1H1, and UBR4. |
Site-directed mutagenesis (point mutations of arginine residues), PRMT5 knockdown/inhibition, in vitro and in vivo methylation assay, eCLIP-seq, RNA binding assays with G4 disruption (LiCl) |
Nucleic acids research |
High |
38709899
|
| 2024 |
FXR1 forms a cytoplasm-spanning mRNA-protein (mRNP) network by packaging exceptionally long mRNAs into condensate scaffolds; this FXR1 network functions as a signaling scaffold for RhoA-induced actomyosin reorganization by providing spatial proximity between kinases and their substrates; FMR1-equivalent point mutations in FXR1 disrupt the network and prevent actomyosin remodeling. |
Super-resolution microscopy, biochemical fractionation, RhoA signaling assays, site-directed mutagenesis (FMR1 disease-equivalent mutations), cell shape and migration assays |
Cell |
High |
39106863
|
| 2024 |
Different RNA motifs (G-quadruplex-containing mRNAs vs. nucleoporin mRNAs) modulate formation of distinct FXR1 condensate subtypes; FXR1 interacts with nuclear pores and the opposing effects of different RNA motifs on FXR1 affinity for nuclear pores determine subcellular condensate localization; reduced FXR1 levels cause nuclear accumulation of transcribed RNAs and facilitate fate transition in human embryonic stem cells. |
Live-cell imaging, nuclear pore co-immunoprecipitation, RNA binding domain mutagenesis, RNA motif competition assays, hESC differentiation assays |
Nature communications |
Medium |
41022782
|
| 2024 |
The muscle-specific isoforms FXR1-G and FXR1-E are required for miR-1-mediated repression of connexin 43 (Cx43) 3′-UTR; FXR1-G promotes physical interaction between miR-1 and the Cx43 3′-UTR; muscle-specific FXR1 isoforms are decreased in pediatric dilated cardiomyopathy left ventricular tissue. |
3′-UTR luciferase reporter, co-immunoprecipitation of miR-1/FXR1/Cx43 mRNA complex, H9c2 differentiation model, Western blot of patient tissue |
American journal of physiology. Heart and circulatory physiology |
Medium |
40323739
|
| 2025 |
SARS-CoV-2 NSP3 binds FXR1 via residues Y138 and F145 in the hypervariable region; NSP3-FXR1 interaction disrupts early stress granule formation; NSP3 Y138A/F145A mutant virus shows reduced replication in vitro and in vivo without altering interferon responses, attributed to loss of stress granule control. |
Reverse genetics mutant virus, in vitro binding assays, in vivo infection model, stress granule imaging |
bioRxivpreprint |
Medium |
bio_10.1101_2025.11.22.689758
|
| 2019 |
FXR1 protein forms amyloid-like aggregates (detergent-resistant, Congo-red birefringent, thioflavine-positive) in cortical neurons of healthy rat brain; RNA molecules co-localizing with FXR1 in these neurons are RNase A-insensitive, suggesting FXR1 functions in amyloid form in the brain. |
Immunoprecipitation from brain tissue, amyloid-specific dye staining (Congo red, Thioflavine S/T), proteomic approach for amyloid-like aggregate isolation |
Scientific reports |
Medium |
31831836
|
| 2025 |
FXR1 colocalizes with core stress granule proteins (TIA-1, FMRP, FXR2, SFPQ) under heat shock and sodium arsenite stress in neuronal cells; in a yeast model, FXR1 physically interacts with these stress granule proteins; FXR1 co-localizes with anti-amyloid antibody OC under normal and stress conditions, suggesting amyloid FXR1-containing RNP particles interact with other stress granule components. |
Immunofluorescence co-localization, yeast two-hybrid/co-localization in yeast model, amyloid antibody staining |
Prion |
Low |
40411539
|
| 2025 |
FXR1 loss in HAP1 cells causes nuclear pore pathology and passive egress of proteins and RNA from the nucleus; TDP-43 cytoplasmic mislocalization upon impaired nuclear import is restricted to FXR1 knockout cells (not FXR2 or FMR1 KO); loss of FXR1 specifically contributes to nuclear pore dysfunction-associated TDP-43 pathology. |
CRISPR KO of individual FXP family members, nuclear pore integrity assays, TDP-43 localization immunofluorescence, nuclear import impairment assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.10.27.684798
|
| 2025 |
FXR1 is an m6A reader protein in HAdV-5-infected cells; FXR1 controls stability of MLTU (major late transcription unit) mRNAs encoding viral capsid proteins; the long FXR1 isoform specifically interferes with MLTU mRNA translation; FXR1 depletion increases MLTU mRNA levels but paradoxically reduces capsid protein and infectious virus production. |
siRNA depletion, m6A-modified mRNA pulldown, mRNA stability assays, isoform-specific overexpression, plaque assays |
Journal of virology |
Medium |
36749074
|
| 2026 |
OTUD6B deubiquitinase stabilizes FXR1 by removing K48-linked polyubiquitin chains via its catalytic activity; OTUD6B binds the KH domain of FXR1; FXR1 in turn binds and stabilizes MEK2 mRNA, activating ERK signaling; FXR1 also upregulates OTUD6B expression, creating a feed-forward oncogenic loop. |
Co-immunoprecipitation, in vitro deubiquitination assay, domain-mapping, mRNA stability assay, RIP, knockdown functional assays |
Cell death & disease |
Medium |
42056075
|
| 2026 |
FXR1 drives alternative splicing of MK5 pre-mRNA to retain exon 6, generating a long kinase-competent isoform (MK5-L) that phosphorylates GSK3β and activates the Wnt/β-catenin pathway in hepatocellular carcinoma; ASO-mediated FXR1 targeting shifts splicing to the inactive MK5-S isoform and suppresses tumor growth. |
RNA-seq splicing analysis, isoform-specific overexpression/knockdown, in vitro/in vivo functional assays, ASO therapeutic model |
Cancer science |
Medium |
41954085
|
| 2024 |
In skeletal muscle, exon-15-containing FXR1 isoform (Fxr1E15+) promotes myogenic differentiation and fusion while exon-15-lacking isoform (Fxr1E15−) regulates myoblast proliferation; increased inclusion of exon 15 during differentiation is mediated by binding of Rbm24 to the intron; the Fxr1E15+ isoform facilitates muscle regeneration in vivo. |
Isoform-specific knockdown in myoblasts, transcriptome and splicing analysis, Rbm24 splice-factor binding assay, in vivo muscle regeneration model |
Advanced science |
Medium |
39499773
|