Affinage

CELF1

CUGBP Elav-like family member 1 · UniProt Q92879

Length
486 aa
Mass
52.1 kDa
Annotated
2026-06-09
84 papers in source corpus 43 papers cited in narrative 43 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

CELF1 (CUG-BP1) is a multifunctional RNA-binding protein that recognizes UGU/GU-rich elements (GREs) through three RRMs to control mRNA deadenylation, decay, translation, and pre-mRNA alternative splicing across development, muscle, and cancer (PMID:16601207, PMID:23748565, PMID:27869122). High-affinity engagement requires UGU-rich stretches of ≥30 nt containing multiple UGU trinucleotides, with all three RRMs simultaneously contacting RNA in a non-sequential 2-1-3 arrangement; this binding mode also explains recognition of dispersed single-stranded UGU sites and CUG-repeat expansions (PMID:16938098, PMID:23748565, PMID:21743084). CELF1 destabilizes target transcripts both by directly recruiting the PARN deadenylase to ARE-containing mRNAs and, in the nucleus, by interacting RNA-independently with the 3'→5' exoribonuclease RRP6 to drive degradation (PMID:16601207, PMID:28874395). CELF1 also acts in translation: it represses targets such as MYC, Cyp19a1/aromatase, and lens regulators (Pax6, Prox1, p27Kip1) by binding their UTRs without changing mRNA levels, and it can translationally activate GRE-containing EMT-driver mRNAs by serving as a non-canonical eIF4E/PABPC1 adaptor that promotes cap-dependent, eIF4G1-independent translation (PMID:25808495, PMID:27869122, PMID:32594240, PMID:26169831, PMID:41755641). CELF1 function is spatially partitioned—nuclear CELF1 drives alternative splicing and skeletal muscle wasting, whereas cytoplasmic CELF1 governs translational targets (PMID:32412585). Activity is post-translationally tuned: PKCα/ε phosphorylation stabilizes CELF1 and is required for its pro-EMT function, while phosphorylation in malignant cells impairs GRE-RNA binding and derepresses growth-promoting transcripts (PMID:39343007, PMID:26249002). Through these activities CELF1 governs spermiogenesis, lens fiber differentiation, somite and cardiac patterning, thermogenic metabolism, and tumor progression (PMID:17130239, PMID:29565969, PMID:22899848, PMID:27144987, PMID:40789858).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established that CELF1 acts as a deadenylation factor and that its RNA-binding activity is separable from its deadenylation-promoting activity, defining a functional dissection of the protein.

    Evidence Cell-free deadenylation assay with RNA-binding-competent, deadenylation-deficient mutant

    PMID:12799066

    Open questions at the time
    • Did not identify the deadenylase recruited
    • No defined target sequence requirement
  2. 2006 High

    Resolved the deadenylation mechanism by showing CELF1 directly recruits the PARN deadenylase to ARE-containing mRNAs, and defined the UGU-rich element requirements that confer functional decay.

    Evidence In vitro deadenylation, co-IP and recombinant reconstitution of CELF1–PARN; SELEX/SPR/EMSA plus in vivo reporter

    PMID:16601207 PMID:16938098

    Open questions at the time
    • Whether PARN is the sole effector deadenylase
    • How element length/motif number is read structurally
  3. 2007 Medium

    Defined CELF1 subcellular dynamics, showing nucleus-to-stress-granule shuttling and co-transcriptional recruitment to nascent RNPs, with the RRM2–RRM3 linker mediating granule/PNC targeting.

    Evidence Immunofluorescence, domain-deletion mutants, lampbrush chromosome immunostaining with tag confirmation

    PMID:18095176 PMID:18164289

    Open questions at the time
    • Signals governing nucleocytoplasmic partitioning not defined
    • Functional consequence of co-transcriptional loading unresolved
  4. 2011 High

    Provided biophysical rules for RNA recognition, showing tandem RRM1+RRM2 bind cooperatively with U-spacer-dependent affinity and distinguishing UGU/CUG selectivity between the two RRMs.

    Evidence NMR titration, ITC, gel filtration, gel retardation of RNA variants

    PMID:21743084

    Open questions at the time
    • RRM3 contribution addressed only in later work
    • Affinity in cellular context not measured
  5. 2013 High

    Determined that all three RRMs simultaneously engage a GU-rich element in a non-sequential 2-1-3 arrangement, providing the structural basis for recognition of both spaced motifs and CUG-repeat hairpins.

    Evidence NMR with paramagnetic relaxation enhancement, ITC, gel retardation

    PMID:23748565

    Open questions at the time
    • No full-length CELF1–RNA structure
    • How structure couples to effector recruitment unknown
  6. 2006 High

    Established an essential developmental role in vivo, showing CELF1 loss arrests spermiogenesis and increases germ cell apoptosis.

    Evidence Constitutive knockout mouse with histology and expression mapping

    PMID:17130239

    Open questions at the time
    • Direct mRNA targets not identified in this study
    • Cell-autonomy across germ/Sertoli/Leydig cells unresolved
  7. 2012 High

    Demonstrated target-specific developmental decay in vivo, with CELF1 driving dmrt2a mRNA degradation to control left-right and somite patterning.

    Evidence Zebrafish RIP plus target-protector morpholino epistasis rescue

    PMID:22899848

    Open questions at the time
    • Decay machinery recruited for dmrt2a not defined
  8. 2013 Medium

    Extended CELF1 to embryonic patterning networks, linking its mRNA repression of rbpj to Notch/FGF/RA coupling and showing roles in endoderm migration via gata5/cdc42.

    Evidence Xenopus and zebrafish morpholino knockdown, RIP, pharmacological epistasis

    PMID:24005864 PMID:24167718

    Open questions at the time
    • Decay vs translational mechanism not always distinguished
    • Morpholino-based; limited rescue
  9. 2015 High

    Established CELF1 as a direct translational repressor in vivo, repressing aromatase (Cyp19a1) to maintain testosterone for spermiogenesis, and MYC via 3'-UTR competition with HuR.

    Evidence Knockout mouse with hormone rescue; RIP, translation reporters, RBP competition assays

    PMID:25808495 PMID:26169831

    Open questions at the time
    • Mechanism of translational block (initiation vs elongation) not defined for these targets
  10. 2016 High

    Identified CELF1 as a post-translationally upregulated, GRE-dependent translational activator of EMT-driver mRNAs that is necessary and sufficient for mesenchymal transition and metastasis.

    Evidence Polyribosomal profiling, RIP, 3'-UTR reporters, in vivo metastasis assays, clinical tissue validation

    PMID:27869122 PMID:29269732

    Open questions at the time
    • How a GRE-binder switches from repression to activation not yet mechanistically defined here
  11. 2017 High

    Revealed a nuclear decay route in which CELF1 recruits the exosome exoribonuclease RRP6 RNA-independently to degrade Cx43 mRNA, and documented GRE-driven decay of pro-apoptotic and secretory transcripts.

    Evidence RIP, NLS mutant, RNA-independent co-IP, knockdown; CLIP and recombinant binding for SRP mRNAs

    PMID:23324604 PMID:28129347 PMID:28874395

    Open questions at the time
    • What determines PARN- vs RRP6-mediated decay of a given target unknown
    • Compartment switch logic incomplete
  12. 2018 High

    Defined distinct mechanistic modes in lens and intestinal cells—translational repression (p27Kip1, p53), transcript stabilization (Dnase2b), and splicing control (beta-spectrin)—linking CELF1 to differentiation and cell-cycle outcomes.

    Evidence Conditional knockout mice, multi-species knockdown, RIP, 5'-UTR/UTR reporters, polysomal profiling, p53 epistasis

    PMID:29565969 PMID:30514107

    Open questions at the time
    • How CELF1 can both stabilize and destabilize different targets in the same cell unresolved
  13. 2020 High

    Demonstrated functional compartmentalization: nuclear CELF1 drives splicing changes and muscle wasting, whereas cytoplasmic CELF1 alters translational targets without histopathology.

    Evidence Doxycycline-inducible compartment-restricted CELF1 transgenic mice, RNA-seq, histopathology; also lens 3'-UTR translational repression of Pax6/Prox1

    PMID:32412585 PMID:32594240

    Open questions at the time
    • Splicing targets driving muscle wasting not fully enumerated
    • Determinants of CELF1 localization not defined
  14. 2021 Medium

    Expanded CELF1's pathophysiological reach in cardiovascular disease, showing direct UTR binding that destabilizes Vegfa, FMO2, and HO-1 mRNAs and represses PEBP1 translation to modulate hypertrophy, fibrosis, and vascular density.

    Evidence RIP, biotin pull-down, 3'-UTR reporters, mRNA stability assays, cardiomyocyte-specific depletion

    PMID:30508596 PMID:33811692 PMID:34669021 PMID:40021568

    Open questions at the time
    • Largely single-lab per target
    • Decay machinery for cardiac targets not defined
  15. 2022 High

    Established a cooperative nuclear splicing partnership with HuR (ELAVL1) and provided the first selective small-molecule strategy to disrupt CELF1–RNA binding therapeutically.

    Evidence FRET-FLIM nuclear interaction, RNAi, exon array; virtual screening, RNA-competition binding assay, in vivo fibrosis model

    PMID:35234905 PMID:35973378

    Open questions at the time
    • Structural basis of inhibitor binding not solved
    • How CELF1/HuR cooperate vs antagonize across targets unclear
  16. 2024 High

    Defined the principal post-translational control of CELF1 stability and a covalent drug mechanism: PKCα/ε phosphorylation stabilizes CELF1 by reducing ubiquitination, and thiopurines covalently modify RRM-proximal cysteines to block RNA binding.

    Evidence MS phosphosite mapping, in vitro kinase assays, phosphomutant/xenograft analysis; biochemical disruption assay with cysteine mutagenesis and reducing-agent rescue

    PMID:39268573 PMID:39343007

    Open questions at the time
    • E3 ligase controlling CELF1 ubiquitination not identified
    • Phosphorylation-driven RNA-binding inhibition in malignancy mechanistically distinct and only correlational (idx 22)
  17. 2026 High

    Identified a non-canonical translation-initiation mechanism, with CELF1 binding eIF4E and PABPC1 to drive eIF4G1-independent cap-dependent translation of GRE-containing EMT effectors, explaining its translational-activator role.

    Evidence Co-IP, in vitro binding, translation reporters, xenograft metastasis model

    PMID:41755641

    Open questions at the time
    • How the same GRE-binder selects activation vs repression contexts unresolved
    • Structure of the CELF1–eIF4E–PABPC1 complex unknown
  18. 2025 Medium

    Connected CELF1 to metabolism and to phase-separation-based splicing control, stabilizing Dio2 mRNA for thermogenesis and forming nuclear condensates (regulated by tRF-24/AKT1 at Ser28) that direct pro-oncogenic BIN1/BECN1 splicing.

    Evidence Adipocyte-specific knockout with metabolic phenotyping and RIP; FRAP, nuclear fractionation, phosphomutant analysis, splicing RNA-seq

    PMID:40789858 PMID:41250205

    Open questions at the time
    • Phase-separation mechanism from single study
    • Link between condensate formation and splice-site selection mechanistically incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular logic determines whether CELF1 represses, activates, or splices a given GRE-containing target, and how phosphorylation, localization, and condensate formation are integrated to switch between these outcomes.
  • No unifying model for activation-vs-repression selection
  • Effector choice (PARN vs RRP6 vs eIF4E) not predictable from sequence
  • Full-length CELF1 structure on functional RNP absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0045182 translation regulator activity 6 GO:0140110 transcription regulator activity 5 GO:0140098 catalytic activity, acting on RNA 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4 GO:0005730 nucleolus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
AKT1EIF4EELAVL1PABPC1PARNPRKCAPRKCERRP6
Complex memberships
stress granulevegetal RNA localization RNP

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CUG-BP1/CELF1 binds specifically to ARE-containing mRNAs (c-fos, TNFα) and stimulates poly(A) shortening by directly recruiting PARN deadenylase; the CELF1–PARN interaction was demonstrated by co-immunoprecipitation from extracts and reconstituted with recombinant proteins. In vitro deadenylation assay, co-immunoprecipitation, recombinant protein pulldown RNA (New York, N.Y.) High 16601207
2003 Human CUG-BP/CELF1 functions as a deadenylation factor in a cell-free deadenylation assay; a mutant form retaining RNA-binding activity but lacking deadenylation function was identified, distinguishing RNA binding from deadenylation activity. In vitro deadenylation assay, RNA-binding assay, mutant analysis Biology of the cell High 12799066
2006 High-affinity CELF1 binding requires UGU-rich sequences of at least 30 nucleotides containing ≥4 UGU trinucleotide motifs; high-affinity binding (but not low-affinity binding) confers deadenylation activity on a reporter mRNA in vivo. SELEX, surface plasmon resonance, EMSA, in vivo deadenylation reporter assay The Biochemical journal High 16938098
2013 Structural analysis by NMR and ITC shows all three RRMs of CELF1 simultaneously engage a 15-nt GU-rich element (5'-UGUNxUGUNyUGU); the three RRMs adopt a non-sequential 2-1-3 arrangement on RNA; CELF1 can also bind dispersed single-stranded UGU sites at the base of an RNA hairpin, explaining recognition of CUG-repeat expansions. NMR (paramagnetic relaxation enhancement), ITC, gel retardation Nucleic acids research High 23748565
2011 NMR titration and ITC show that RRM1 binds both UGU and CUG repeats promiscuously, while RRM2 selects UGUU over CUG; cooperative high-affinity binding (Kd ~0.4 µM) by tandem RRM1+RRM2 requires a 2–4 U spacer between UGU sites; longer spacers (≥5 U) reduce affinity 10-fold. NMR titration, ITC, gel filtration, gel retardation Nucleic acids research High 21743084
2007 CELF1 localizes to stress granules (SGs) under environmental stress and shuttles between the nucleus and SGs; the linker domain between RRM2 and RRM3 is required for recruitment to both SGs and the perinucleolar compartment (PNC). Immunofluorescence, domain-deletion mutant analysis, live-cell imaging Experimental cell research Medium 18164289
2007 CELF1 is co-transcriptionally recruited to nascent RNPs on lampbrush chromosome transcription units in amphibian oocytes; exogenous myc-tagged CUG-BP1 targets the same loci as endogenous CELF1 when expressed in microinjected oocytes. Immunostaining of lampbrush chromosome spreads, microinjection of tagged protein Chromosome research Medium 18095176
2006 CELF1 knockout in mice causes spermatogenesis arrest at step 7 of spermiogenesis (before spermatid elongation), increased apoptosis of germ cells, and growth retardation; CUG-BP1 is expressed in spermatogonia through round spermatids and in Sertoli and Leydig cells. Homologous recombination knockout, histology, RT-qPCR Molecular and cellular biology High 17130239
2015 CELF1 directly binds the 3'-UTR of Myc mRNA and represses MYC translation without affecting total Myc mRNA levels; CELF1 and HuR compete for binding to the same Myc 3'-UTR element, with each protein antagonizing the other's association with the mRNA. RNA immunoprecipitation, translation reporter assay, RBP competition assay, siRNA knockdown, ectopic overexpression Molecular biology of the cell High 25808495
2017 CELF1 mediates Cx43 (connexin 43) mRNA degradation by binding the UG-rich element in the Cx43 3'-UTR; nuclear localization of CELF1 is required for this activity; CELF1 interacts with the 3'→5' exoribonuclease RRP6 in an RNA-independent, nucleus-specific manner, and RRP6 knockdown abolishes CELF1-mediated Cx43 mRNA degradation. RNA immunoprecipitation, nuclear localization signal mutation, co-immunoprecipitation, siRNA knockdown Circulation research High 28874395
2017 CELF1 binds GU-rich elements in the 3'-UTRs of pro-apoptotic mRNAs BAD, BAX, and JunD and mediates their rapid mRNA decay; silencing CELF1 stabilizes these mRNAs and increases their protein expression in oral cancer cells. RNA immunoprecipitation, 3'-UTR reporter assay, siRNA knockdown, mRNA half-life assay RNA biology Medium 23324604
2016 CELF1 binds GU-rich cis-elements in the 3'-UTRs of EMT driver mRNAs and promotes their translation; CELF1 protein (but not mRNA) is post-translationally up-regulated during EMT; CELF1 is necessary and sufficient for mesenchymal transition and metastatic colonization. Polyribosomal profiling, 3'-UTR reporter assay, RNA immunoprecipitation, loss-of-function/gain-of-function experiments, metastasis assays Nature communications High 27869122
2018 Celf1 post-transcriptionally regulates p27Kip1 by binding its 5'-UTR and inhibiting translation, and maintains high Dnase2b mRNA levels by direct binding; together these control Cdk1-mediated lamin A/C phosphorylation to initiate nuclear envelope breakdown and DNA degradation in lens fiber cells. Celf1 also regulates alternative splicing of beta-spectrin and Actn2 mRNA levels to control fiber cell morphology. Conditional knockout mice, knockdown in zebrafish and Xenopus, RNA immunoprecipitation, 5'-UTR translation reporter assay PLoS genetics High 29565969
2020 Celf1 post-transcriptionally regulates Pax6 and Prox1 protein expression in lens development via their 3'-UTRs without affecting mRNA levels; Celf1 protein directly binds Pax6 and Prox1 transcripts as shown by RIP; reporter assays in Celf1 knockdown and overexpression cells confirm translational repression. Lens-conditional knockout mice, immunostaining, RT-qPCR, RNA immunoprecipitation, 3'-UTR reporter assay Human genetics High 32594240
2015 CELF1 directly represses Cyp19a1 (aromatase) translation by binding its mRNA; CELF1 deficiency causes elevated aromatase, reduced testosterone, and spermiogenesis failure in mice; testosterone or aromatase inhibitor administration partially rescues the phenotype. Knockout mouse model, in vivo and in vitro CELF1-mRNA interaction assay, translation reporter assay, hormone rescue experiment Molecular and cellular biology High 26169831
2012 Celf1 promotes dmrt2a mRNA decay in zebrafish by binding UGU repeats in its 3'-UTR; blocking the Celf1–dmrt2a mRNA interaction with a target protector morpholino rescues somite symmetry and left-right patterning defects caused by celf1 overexpression. Zebrafish overexpression/morpholino knockdown, RNA immunoprecipitation, target protector morpholino epistasis Development (Cambridge, England) High 22899848
2013 In zebrafish, Celf1 binds gata5 and cdc42 mRNAs (involved in cell growth and migration) as shown by RIP; celf1 morpholino knockdown causes endoderm cell growth and migration defects leading to failure of liver bud formation and aberrant pancreas bud organization. Morpholino knockdown, RNA immunoprecipitation International journal of molecular sciences Medium 24005864
2013 In Xenopus somite segmentation, Celf1 targets rbpj mRNA for rapid degradation; derepression of rbpj in celf1 morphants stimulates Notch signaling, induces cyp26a overexpression, attenuates retinoic acid (RA) signaling, and represses fgf8—linking Celf1-mediated post-transcriptional repression to FGF–RA pathway coupling. Morpholino knockdown, epistasis, pharmacological pathway inhibition, RT-qPCR Biology open Medium 24167718
2015 In Xenopus oogenesis, Celf1 is a component of vegetal RNA localization RNP complexes; it shows specific interactions with localization elements (LEs) from several vegetally localizing RNAs; overexpression of Celf1 or mutation of its LE binding sites interferes with vegetal RNA localization. RNA affinity purification, immunostaining, co-localization, morpholino/overexpression functional assays Developmental biology Medium 26164657
2020 Nuclear CELF1 activity, but not cytoplasmic CELF1 activity, is responsible for skeletal muscle wasting; transgenic mice expressing nuclear-restricted CELF1 show strong histopathological defects, muscle loss, and alternative splicing changes within 10 days, whereas cytoplasmic-restricted CELF1 causes translational target protein changes without histopathology. Doxycycline-inducible transgenic mice with compartment-restricted CELF1 mutants, RNA-sequencing, histopathology Human molecular genetics High 32412585
2016 CELF1 directly binds GRE-containing 3'-UTRs of EMT driver mRNAs to translationally activate them; CELF1 protein (but not mRNA) is regulated post-translationally (by PKC-mediated phosphorylation) during EMT; CELF1 was identified as a novel regulator of the DEK oncogene in melanoma through RNA-immunoprecipitation and transcriptomic analyses. Genome-wide RNA-immunoprecipitation, proteomics, loss-of-function in cell lines, transcriptomic analysis Nature communications Medium 29269732
2024 PKCα and PKCε phosphorylate CELF1 at multiple serine/threonine residues, increasing CELF1 stability and decreasing its ubiquitination; phosphomimetic CELF1 mutants are more stable and functional in EMT than phospho-null mutants; genetic epistasis places PKCα/ε upstream of CELF1 in the EMT program. Mass spectrometry of CELF1 phosphosites, co-immunoprecipitation, in vitro kinase assay, phosphomutant analysis, xenograft metastasis model The Journal of biological chemistry High 39343007
2015 CELF1 phosphorylation in malignant T cells prevents binding to GRE-containing mRNAs that serve as CELF1 targets in normal T cells, resulting in stabilization and up-regulation of these growth-promoting transcripts; lack of CELF1 binding correlates with loss of normal mRNA decay function. Anti-CELF1 immunoprecipitation with microarray of co-purified transcripts, phosphorylation analysis RNA (New York, N.Y.) Medium 26249002
2022 CELF1 and ELAVL1 (HuR) directly interact in the nucleus (shown by FRET-FLIM) and cooperatively stimulate inclusion of CD44 variable exons v7–v10; depletion of either protein reduces exon inclusion. FRET-FLIM, RNAi depletion, exon array, RT-PCR Biochemical and biophysical research communications High 35973378
2021 CELF1 directly binds PEBP1 mRNA 3'-UTR fragment 1 and negatively regulates PEBP1 protein (without affecting mRNA levels), activating the MAPK (Raf1/TAK1/ERK1/2/p38) signaling pathway to promote cardiac hypertrophy. RNA immunoprecipitation, biotin pull-down, dual-luciferase assay, siRNA/overexpression, ROS and apoptosis assays Cell and tissue research Medium 34669021
2021 CELF1 binds Vegfa mRNA via its 3'-UTR and promotes its decay; cardiomyocyte-specific CELF1 depletion in infarcted hearts preserves Vegfa mRNA levels and capillary density, linking CELF1-mediated mRNA destabilization to vascular rarefaction in DCM. RNA immunoprecipitation, 3'-UTR reporter assay, cardiomyocyte-specific CELF1 depletion, capillary density measurement FASEB journal Medium 33811692
2017 CELF1 directly binds all six SRP subunit mRNAs in myoblasts (by CELF1 CLIP and in vitro binding with recombinant CELF1) and destabilizes at least five of the six Srp transcripts; CELF1 knockdown causes SRP protein imbalance, impairs secretion, and reduces myoblast wound-healing/migration. CLIP-seq, in vitro binding with recombinant CELF1, mRNA half-life assay, siRNA knockdown, secretion/migration assays PloS one High 28129347
2018 CELF1 binds conserved GU-rich elements (GREs) in the HO-1 3'-UTR and destabilizes HO-1 mRNA; CO (a product of HO-1) in turn regulates CELF1 expression, forming a positive feedback circuit in cardiac myoblasts. RNA immunoprecipitation (RIP-seq), biotin pull-down, luciferase reporter, mRNA stability assay Biochimica et biophysica acta. Gene regulatory mechanisms Medium 30508596
2018 CELF1 contributes to aberrant alternative splicing in the type 1 diabetic heart; disruption of CELF1 binding sites impairs CELF1-mediated alternative splicing regulation of relevant target genes. RNA-seq, genome-wide alternative splicing analysis, CELF1 binding site mutation Biochemical and biophysical research communications Medium 30158053
2016 CELF1 knockdown in primary embryonic cardiomyocytes results in increased inclusion of a novel unannotated exon in MYH7B and decreased MYH7B protein levels; CLIP identified this exon as a direct CELF1 binding target in embryonic hearts. Cross-linking immunoprecipitation (CLIP), siRNA knockdown, RT-PCR, RNA-seq PloS one Medium 26866591
2016 In Xenopus embryos and chicken cardiomyocytes, Celf1 knockdown causes myofibrillar disorganization, reduced proliferation, morphogenetic abnormalities, and impaired cardiac contraction without affecting heart rhythm; loss of Celf1 does not disrupt myofibril organization in skeletal muscle but does cause skeletal muscle bundle fragmentation. Morpholino knockdown (Xenopus), siRNA knockdown (chicken primary cardiomyocytes), optical coherence tomography, immunofluorescence Developmental dynamics Medium 27144987
2015 Celf1 overexpression in myoblasts increases cell cycling and largely recapitulates CUG-expansion differentiation defects; knockdown of endogenous Celf1 leads to precocious myotube formation; Celf1 knockdown in CUG-expansion myocytes partially rescues the differentiation defect by promoting cell cycle exit. Overexpression, siRNA knockdown, cell cycle analysis, myocyte differentiation assays Biochimica et biophysica acta Medium 25887157
2014 CELF1 target transcripts containing GREs in their 3'-UTRs undergo preferential 3'-end shortening by alternative polyadenylation (APA) following T cell activation, reducing inclusion of CELF1 binding sites and increasing transcript expression; CELF1 reversibly binding nearby GRE sequences can regulate APA site selection. Global RNA sequencing, APA analysis, CELF1 binding site mapping Gene Medium 25123787
2022 Small molecule compound 27 directly binds CELF1 and competes with RNA for binding to CELF1, disrupting CELF1-RNA interaction; this inhibits CELF1-mediated IFN-γ mRNA decay in hepatic stellate cells and attenuates liver fibrosis in vivo; compound 841, a derivative, was identified as a selective CELF1 inhibitor. Virtual screening, biochemical binding assay, RNA competition assay, siRNA knockdown, mouse liver fibrosis model Nucleic acids research High 35234905
2024 Thiopurine drugs (6-mercaptopurine, 6-thioguanine) disrupt CELF1-RNA interaction by forming disulfide bonds with cysteine residues proximal to CELF1's RNA recognition motifs; mutation of this cysteine or addition of reducing agents abolishes the disrupting activity. Biochemical CELF1-RNA disruption assay, site-directed mutagenesis, reducing agent controls, cell-based myogenesis assay Nucleic acids research High 39268573
2025 CELF1 binds the 3'-UTR of Dio2 mRNA and enhances its stability, promoting local T3 production and thermogenic gene expression in beige adipocytes; adipocyte-specific Celf1 knockout impairs cold-induced thermogenesis and reduces energy expenditure. Adipocyte-specific knockout mice, RNA immunoprecipitation, mRNA stability assay, metabolic phenotyping Nature communications High 40789858
2018 CELF1 promotes p53 protein translation (not mRNA level) in intestinal epithelial cells, as demonstrated by polysomal profiling and nascent protein analysis; ectopic CELF1 overexpression causes sustained G2 or G1 arrest in a p53-dependent manner, with p53 silencing abolishing the arrest. Polysomal profiling, nascent protein analysis, cell cycle assay, p53 siRNA epistasis, overexpression/knockdown FASEB journal High 30514107
2024 CELF1 directly binds KLC1 RNA (established by CLIP-seq database) and down-regulates KLC1 splice variant E (KLC1_vE) formation; depletion and overexpression experiments in cultured cells confirm that CELF1 protein reduces KLC1_vE levels, likely by modulating terminal exon usage. CLIP-seq (database), siRNA depletion, CELF1 overexpression, transcriptomic analysis Biochemical and biophysical research communications Medium 38768546
2026 CELF1 acts as a non-canonical eIF4E-binding protein; it directly binds both eIF4E and PABPC1 to promote eIF4G1-independent translation of GRE-containing EMT effector mRNAs in mesenchymal cells; disruption of the CELF1/eIF4E interaction inhibits EMT induction in vitro and experimental metastasis in vivo. Co-immunoprecipitation, in vitro binding, translation reporter assay, xenograft metastasis model Nucleic acids research High 41755641
2026 iCLIP-seq in mouse lenses maps CELF1 binding primarily to 3'-UTRs of key lens transcripts (including Gja8, Jag1, Maf, Pax6, Prox1); integrated transcriptomic and luciferase reporter data show CELF1 represses target mRNAs by destabilizing transcripts and/or inhibiting translation; cataract-linked genes Maf and Gja8 are up-regulated in Celf1 cKO lenses; Maf overexpression in Xenopus causes abnormal lens structure. iCLIP-seq, conditional knockout transcriptomics, luciferase reporter assay, Xenopus overexpression bioRxivpreprint High 41542625
2025 CELF1 directly binds FMO2 mRNA 3'-UTR (via biotinylated GU-rich element pull-down and RIP) and promotes FMO2 mRNA decay; CELF1 silencing up-regulates FMO2 and improves post-myocardial infarction cardiac remodeling, while FMO2 overexpression reverses ECM deposition worsened by CELF1 activity. RNA immunoprecipitation, RNA pull-down (biotinylated 3'-UTR), actinomycin D mRNA stability assay, in vivo cardiac model Cardiovascular toxicology Medium 40021568
2020 CELF1 regulates ETS2 mRNA stability by binding its 3'-UTR, as demonstrated by luciferase reporter and ribonucleoprotein immunoprecipitation assays; CELF1 overexpression increases CRC cell proliferation, migration, invasion, and resistance to oxaliplatin, and ETS2 knockdown reverses the drug resistance induced by CELF1 overexpression. Luciferase reporter assay, RIP, CELF1 overexpression/knockdown, xenograft model Clinical science Medium 32677671
2025 tRF-24 binds CELF1 at Ser28, inhibiting AKT1-mediated phosphorylation at this site, which promotes CELF1 nuclear translocation and liquid-liquid phase separation (LLPS) formation; CELF1-enriched nuclear condensates regulate alternative splicing of BIN1 and BECN1 pre-mRNAs, generating pro-oncogenic isoforms. RNA pull-down, fluorescence recovery after photobleaching (FRAP), nuclear fractionation, phosphomutant analysis, RNA-seq/alternative splicing analysis Journal of experimental & clinical cancer research Medium 41250205

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The importance of CELF control: molecular and biological roles of the CUG-BP, Elav-like family of RNA-binding proteins. Wiley interdisciplinary reviews. RNA 195 22180311
2006 CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA (New York, N.Y.) 153 16601207
2017 CELF1 preferentially binds to exon-intron boundary and regulates alternative splicing in HeLa cells. Biochimica et biophysica acta. Gene regulatory mechanisms 140 28733224
2006 Inactivation of CUG-BP1/CELF1 causes growth, viability, and spermatogenesis defects in mice. Molecular and cellular biology 100 17130239
2016 Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2. BMC cancer 95 27485439
2015 Competition between RNA-binding proteins CELF1 and HuR modulates MYC translation and intestinal epithelium renewal. Molecular biology of the cell 77 25808495
2006 CUG-BP1/CELF1 requires UGU-rich sequences for high-affinity binding. The Biochemical journal 75 16938098
2013 High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines. Human molecular genetics 64 24179176
2012 CUG-BP, Elav-like family (CELF)-mediated alternative splicing regulation in the brain during health and disease. Molecular and cellular neurosciences 61 23247071
2011 Coordinate regulation of mRNA decay networks by GU-rich elements and CELF1. Current opinion in genetics & development 59 21497082
2016 CELF1 is a central node in post-transcriptional regulatory programmes underlying EMT. Nature communications 57 27869122
2018 The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development. PLoS genetics 49 29565969
2013 Overexpression of RNA-binding protein CELF1 prevents apoptosis and destabilizes pro-apoptotic mRNAs in oral cancer cells. RNA biology 49 23324604
2003 A functional deadenylation assay identifies human CUG-BP as a deadenylation factor. Biology of the cell 48 12799066
2017 CELF1 Mediates Connexin 43 mRNA Degradation in Dilated Cardiomyopathy. Circulation research 40 28874395
2007 Dual localization of the RNA binding protein CUGBP-1 to stress granule and perinucleolar compartment. Experimental cell research 36 18164289
2020 RNA-binding protein CELF1 enhances cell migration, invasion, and chemoresistance by targeting ETS2 in colorectal cancer. Clinical science (London, England : 1979) 34 32677671
2014 Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 33 24788522
2016 Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1) Regulation in Embryonic Heart Muscle. PloS one 28 26866591
2013 Structural insights into the targeting of mRNA GU-rich elements by the three RRMs of CELF1. Nucleic acids research 28 23748565
2013 Evaluating the effects of CELF1 deficiency in a mouse model of RNA toxicity. Human molecular genetics 28 24001600
2022 Small molecule targeting CELF1 RNA-binding activity to control HSC activation and liver fibrosis. Nucleic acids research 27 35234905
2021 LncRNA BACE1-AS enhances the invasive and metastatic capacity of hepatocellular carcinoma cells through mediating miR-377-3p/CELF1 axis. Life sciences 27 33667514
2021 Circular RNA CELF1 drives immunosuppression and anti-PD1 therapy resistance in non-small cell lung cancer via the miR-491-5p/EGFR axis. Aging 25 34788230
2015 Celf1 regulates cell cycle and is partially responsible for defective myoblast differentiation in myotonic dystrophy RNA toxicity. Biochimica et biophysica acta 25 25887157
2014 Alternative polyadenylation regulates CELF1/CUGBP1 target transcripts following T cell activation. Gene 24 25123787
2020 The cataract-linked RNA-binding protein Celf1 post-transcriptionally controls the spatiotemporal expression of the key homeodomain transcription factors Pax6 and Prox1 in lens development. Human genetics 21 32594240
2011 Sequence determinants for the tandem recognition of UGU and CUG rich RNA elements by the two N--terminal RRMs of CELF1. Nucleic acids research 20 21743084
2020 MiR-330-3p functions as a tumor suppressor that regulates glioma cell proliferation and migration by targeting CELF1. Archives of medical science : AMS 19 32864006
2018 CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart. Biochemical and biophysical research communications 19 30158053
2017 Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1. Nature communications 19 29269732
2016 Identification of CELF1 RNA targets by CLIP-seq in human HeLa cells. Genomics data 19 27222809
2016 Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1. Scientific reports 19 27759042
2015 CELF1 is Up-Regulated in Glioma and Promotes Glioma Cell Proliferation by Suppression of CDKN1B. International journal of biological sciences 19 26535026
2021 DLX6-AS1 activated by H3K4me1 enhanced secondary cisplatin resistance of lung squamous cell carcinoma through modulating miR-181a-5p/miR-382-5p/CELF1 axis. Scientific reports 18 34697393
2020 Increased nuclear but not cytoplasmic activities of CELF1 protein leads to muscle wasting. Human molecular genetics 17 32412585
2018 MicroRNA-20a Regulates Glioma Cell Proliferation, Invasion, and Apoptosis by Targeting CUGBP Elav-Like Family Member 2. World neurosurgery 17 30268547
2013 Si-RNA mediated knockdown of CELF1 gene suppressed the proliferation of human lung cancer cells. Cancer cell international 17 24237593
2021 RNA-binding protein CELF1 promotes cardiac hypertrophy via interaction with PEBP1 in cardiomyocytes. Cell and tissue research 16 34669021
2015 Hypogonadism Associated with Cyp19a1 (Aromatase) Posttranscriptional Upregulation in Celf1 Knockout Mice. Molecular and cellular biology 15 26169831
2024 Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review. Cellular & molecular biology letters 14 38443798
2012 Alternative splicing of the neurofibromatosis type 1 pre-mRNA is regulated by the muscleblind-like proteins and the CUG-BP and ELAV-like factors. BMC molecular biology 14 23227900
2023 High-Throughput Transcriptomics of Celf1 Conditional Knockout Lens Identifies Downstream Networks Linked to Cataract Pathology. Cells 13 37048143
2022 The RNA-binding proteins CELF1 and ELAVL1 cooperatively control the alternative splicing of CD44. Biochemical and biophysical research communications 13 35973378
2022 Distribution of alternative untranslated regions within the mRNA of the CELF1 splicing factor affects its expression. Scientific reports 12 34996980
2015 A novel role for Celf1 in vegetal RNA localization during Xenopus oogenesis. Developmental biology 12 26164657
2015 Altered CELF1 binding to target transcripts in malignant T cells. RNA (New York, N.Y.) 12 26249002
2012 Celf1 regulation of dmrt2a is required for somite symmetry and left-right patterning during zebrafish development. Development (Cambridge, England) 12 22899848
2021 CELF1 promotes vascular endothelial growth factor degradation resulting in impaired microvasculature in heart failure. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 33811692
2018 A positive feedback regulation of Heme oxygenase 1 by CELF1 in cardiac myoblast cells. Biochimica et biophysica acta. Gene regulatory mechanisms 11 30508596
2017 The CELF1 RNA-Binding Protein Regulates Decay of Signal Recognition Particle mRNAs and Limits Secretion in Mouse Myoblasts. PloS one 11 28129347
2012 Inactivation of the Celf1 gene that encodes an RNA-binding protein delays the first wave of spermatogenesis in mice. PloS one 11 23056285
2007 Localized co-transcriptional recruitment of the multifunctional RNA-binding protein CELF1 by lampbrush chromosome transcription units. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 11 18095176
2017 Supplementary choline attenuates olive oil lipid emulsion-induced enterocyte apoptosis through suppression of CELF1/AIF pathway. Journal of cellular and molecular medicine 10 29105957
2023 Members of the CUGBP Elav-like family of RNA-binding proteins are expressed in distinct populations of primary sensory neurons. The Journal of comparative neurology 7 37537886
2021 SP1-induced AFAP1-AS1 contributes to proliferation and invasion by regulating miR-497-5p/CELF1 pathway in nasopharyngeal carcinoma. Human cell 7 33400247
2020 The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration in Caenorhabditis elegans. G3 (Bethesda, Md.) 7 32398235
2018 CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 30514107
2017 Olive Oil-Supplemented Lipid Emulsion Induces CELF1 Expression and Promotes Apoptosis in Caco-2 Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 7 28214850
2015 Identification of transcripts regulated by CUG-BP, Elav-like family member 1 (CELF1) in primary embryonic cardiomyocytes by RNA-seq. Genomics data 7 26366374
2013 Celf1 is required for formation of endoderm-derived organs in zebrafish. International journal of molecular sciences 7 24005864
2020 Promoting role of circ-Jarid2/miR-129-5p/Celf1 axis in cardiac hypertrophy. Gene therapy 6 32632266
2016 CUG-BP, Elav-like family member 1 (CELF1) is required for normal myofibrillogenesis, morphogenesis, and contractile function in the embryonic heart. Developmental dynamics : an official publication of the American Association of Anatomists 6 27144987
2023 Relationship Between FERMT2, CELF1, COPI, CHRNA2, and ABCA7 Genetic Polymorphisms and Alzheimer's Disease Risk in the Southern Chinese Population. Journal of Alzheimer's disease reports 5 38025799
2025 The RNA-binding protein CELF1 targets ATG5 to regulate autophagy and promote drug resistance in acute myeloid leukemia. Cell death & disease 4 40781108
2025 Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA. Nature communications 4 40789858
2022 CELF1 Selectively Regulates Alternative Splicing of DNA Repair Genes Associated With Cataract in Human Lens Cell Line. Biochemical genetics 4 36585568
2021 miR-322/miR-503 clusters regulate defective myoblast differentiation in myotonic dystrophy RNA-toxic by targeting Celf1. Toxicology research 3 33613970
2025 A novel feedback loop: CELF1/circ-CELF1/BRPF3/KAT7 in cardiac fibrosis. Acta pharmaceutica Sinica. B 2 41132846
2024 Gene-gene functional relationships in Alzheimer's disease: CELF1 regulates KLC1 alternative splicing. Biochemical and biophysical research communications 2 38768546
2024 PKC-mediated phosphorylation governs the stability and function of CELF1 as a driver of EMT in breast epithelial cells. The Journal of biological chemistry 2 39343007
2013 A gene regulation network controlled by Celf1 protein-rbpj mRNA interaction in Xenopus somite segmentation. Biology open 2 24167718
2025 CUGBP Elav-like family member 4 promotes cardiac remodeling through Inhibition of FMO2. BMC cardiovascular disorders 1 40610856
2024 Identification of an RNA-binding perturbing characteristic for thiopurine drugs and their derivatives to disrupt CELF1-RNA interaction. Nucleic acids research 1 39268573
2022 CELF1 represses Doublesex1 expression via its 5' UTR in the crustacean Daphnia magna. PloS one 1 36240182
2026 Mapping of CELF1-RNA interactions reveals post-transcriptional control of lens development. bioRxiv : the preprint server for biology 0 41542625
2026 CELF1 Downregulation Promotes Cardiomyocyte Hypertrophy via Regulating Alternative Splicing of Tead1. Genes 0 41751542
2026 CELF1 is a non-canonical eIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs. Nucleic acids research 0 41755641
2025 A small interfering RNA inhibits lung fibroblast-myofibroblast differentiation via simultaneously knockingdown CELF1 and activating RIG-I signalling. Biochimica et biophysica acta. Molecular cell research 0 39993608
2025 CELF1 Promotes Post-myocardial Infarction Cardiac Remodeling Via Suppression of FMO2. Cardiovascular toxicology 0 40021568
2025 tRNA-derived fragment tRF-24 drives CELF1 phase separation to promote oncogenic splicing in esophageal squamous cell carcinoma. Journal of experimental & clinical cancer research : CR 0 41250205
2025 MiR-23a represses CELF1 to modulate buffalo granulosa cell apoptosis and steroidogenesis via the PI3K/AKT pathway. Animal reproduction science 0 41252912
2025 CELF1 promotes aerobic glycolysis and an aggressive phenotype in ER-positive breast cancer via GLUT1 regulation. Frontiers in genetics 0 41306913
2023 Erratum: CELF1 is Up-Regulated in Glioma and Promotes Glioma Cell Proliferation by Suppression of CDKN1B: Erratum. International journal of biological sciences 0 36778121

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