Affinage

EIF4A3

Eukaryotic initiation factor 4A-III · UniProt P38919

Length
411 aa
Mass
46.9 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF4A3 is a DEAD-box RNA helicase that serves as the central RNA-binding platform of the exon junction complex (EJC), coupling pre-mRNA splicing to downstream mRNA fate including nonsense-mediated decay (NMD), mRNA nuclear export, and translational regulation (PMID:15034551, PMID:16170325, PMID:25313076). During splicing, the spliceosomal factor CWC22 delivers eIF4A3 to the spliceosome in an inactive conformation by holding its RecA domains apart, preventing premature RNA binding; upon EJC assembly, the MAGOH–Y14 heterodimer inhibits eIF4A3 ATPase activity to lock the complex onto RNA, while MLN51 stimulates its helicase activity (PMID:22961380, PMID:24218557, PMID:16170325, PMID:17375189). Beyond the EJC, eIF4A3 functions in pre-rRNA processing and ribosome biogenesis through R-loop resolution in nucleoli, drives internal ribosome entry on circular RNAs via direct eIF4A3–eIF3g interaction, regulates autophagy through TFEB cytoplasmic retention, and—independently of RNA or the EJC—directly binds and polymerizes microtubules to promote axon growth in neurons (PMID:34348895, PMID:37811880, PMID:34643458, PMID:39182224). Loss-of-function mutations, including 5′ UTR repeat expansions that reduce EIF4A3 expression, cause Richieri-Costa–Pereira syndrome through defective neural crest cell migration and craniofacial development (PMID:24360810, PMID:28334780).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing that eIF4AIII is an active RNA helicase distinct from eIF4AI resolved whether paralog diversification produced functional divergence: eIF4AIII possesses RNA-dependent ATPase and helicase activities but cannot substitute for eIF4AI in cap-dependent translation initiation and instead inhibits translation.

    Evidence In vitro ATPase, helicase, 40S ribosome binding reconstitution, and reticulocyte lysate translation assays

    PMID:10523622

    Open questions at the time
    • Cellular role of eIF4AIII undefined
    • Reason for translation inhibition unknown
    • Native RNA substrates unidentified
  2. 2004 High

    Identifying eIF4AIII as the core RNA-binding component of the EJC answered the fundamental question of what anchors the complex to spliced mRNAs and linked eIF4AIII to NMD, redefining its cellular function from a putative translation factor to a post-splicing mRNA fate regulator.

    Evidence Crosslinking, antibody inhibition, Co-IP, siRNA knockdown with NMD reporter in mammalian and Drosophila cells across three concurrent studies

    PMID:14973490 PMID:15024115 PMID:15034551

    Open questions at the time
    • How eIF4AIII is specifically recruited to the EJC during splicing unknown
    • Minimal components for stable EJC not defined
    • Role of ATPase activity in EJC formation unclear
  3. 2005 High

    Reconstituting the minimal EJC core from four purified proteins established that MAGOH–Y14 inhibition of eIF4AIII ATPase locks the complex onto RNA, providing the mechanistic basis for EJC stability on mRNA.

    Evidence In vitro reconstitution with recombinant eIF4AIII, MAGOH, Y14, MLN51; ATPase assay, RNase protection

    PMID:16170325

    Open questions at the time
    • How eIF4AIII is loaded onto spliceosomes before EJC assembly unknown
    • Role of MLN51 in helicase stimulation not yet quantified
  4. 2006 High

    Systematic mutagenesis of eIF4AIII helicase motifs revealed that ATP hydrolysis is dispensable for EJC formation and NMD, while specific eIF4AIII-unique motifs including an MLN51-binding surface are essential, distinguishing the structural scaffolding role from enzymatic activity.

    Evidence Site-directed mutagenesis with EJC formation and NMD rescue assays after RNAi depletion

    PMID:16495234

    Open questions at the time
    • ATPase-independent mechanism of EJC assembly not structurally resolved
    • Whether ATPase activity matters for non-EJC functions unknown
  5. 2007 High

    Quantitative enzymology showed MLN51 activates eIF4AIII helicase by decreasing ATP KM 10-fold and increasing kcat 30-fold, while MAGOH–Y14 partially counteracts this stimulation, revealing a kinetic tug-of-war that governs EJC dynamics.

    Evidence In vitro ATPase and helicase kinetic assays with purified proteins

    PMID:17375189

    Open questions at the time
    • Physiological consequence of MLN51-stimulated vs. MAGOH-Y14-inhibited states not tested in cells
    • Whether helicase activity is needed for EJC remodeling or disassembly unknown
  6. 2007 High

    Immunodepletion experiments demonstrated that eIF4AIII is dispensable for splicing catalysis itself but essential for splicing-dependent EJC loading, temporally placing EJC assembly at late spliceosomal stages requiring the helicase hPrp22.

    Evidence Immunodepletion from HeLa nuclear extract with in vitro splicing assay

    PMID:17606899

    Open questions at the time
    • Factor that recruits eIF4AIII to the spliceosome not identified
    • Mechanism of hPrp22 requirement unresolved
  7. 2011 High

    Identification of eIF4AIII in a complex with the eIF4G-like protein NOM1, and its functional complementation of yeast Fal1, established a conserved EJC-independent role in pre-rRNA processing and ribosome biogenesis.

    Evidence Co-IP, yeast complementation of fal1Δ lethality and 18S rRNA processing defect, RNAi in human cells

    PMID:21576267

    Open questions at the time
    • Mechanism by which eIF4AIII/NOM1 processes pre-rRNA (e.g., R-loop resolution) not yet shown
    • Whether this function is regulated independently of EJC unknown
  8. 2012 High

    Identification of CWC22 as the spliceosomal factor that delivers eIF4AIII to spliceosomes while preventing premature RNA binding answered the long-standing question of how eIF4AIII is specifically channeled into EJC assembly.

    Evidence Recombinant protein pulldown, in vitro splicing, CWC22 knockdown abolishing EJC assembly in vivo

    PMID:22961380

    Open questions at the time
    • Structural basis of CWC22-mediated inhibition not yet solved
    • How CWC22 releases eIF4AIII for EJC formation unknown
  9. 2013 High

    The 2.0-Å crystal structure of eIF4AIII–CWC22-MIF4G revealed that CWC22 holds the two RecA domains in a diametrically opposed, inactive orientation, providing the atomic mechanism by which CWC22 prevents nonspecific RNA binding during spliceosomal transit.

    Evidence X-ray crystallography at 2.0-Å resolution with functional validation

    PMID:24218557

    Open questions at the time
    • Structure of full spliceosomal intermediate with eIF4AIII–CWC22 not captured
    • Conformational transition from CWC22-bound to EJC-bound state not resolved
  10. 2013 High

    Genetic mapping of 5′ UTR repeat expansions in EIF4A3 as the cause of Richieri-Costa–Pereira syndrome, with reduced transcript levels in patients and craniofacial phenocopy in zebrafish, established the first human disease caused by EJC core dysfunction.

    Evidence Identity-by-descent mapping, patient sequencing, qRT-PCR, zebrafish morpholino knockdown

    PMID:24360810

    Open questions at the time
    • Mechanism by which repeat expansion reduces transcription unresolved
    • Whether NMD, ribosome biogenesis, or other eIF4A3 functions drive disease pathology unclear
  11. 2014 High

    Discovery that eIF4AIII is recruited to CBC-bound mRNAs via CTIF, independent of splicing, to unwind 5′ UTR structures demonstrated an EJC-independent translation enhancement function.

    Evidence Polysome fractionation, tethering assay, in vitro reconstitution with recombinant proteins, Co-IP

    PMID:25313076

    Open questions at the time
    • Which mRNAs preferentially depend on CBC-dependent eIF4AIII unwinding undefined
    • Relationship to steady-state eIF4F-dependent translation not clarified
  12. 2017 High

    Patient iPSC-derived neural crest cells and Eif4a3 haploinsufficient mice revealed that RCPS craniofacial defects arise from defective NCC migration and altered osteochondrogenic differentiation, specifying the developmental cell type and process underlying the disease.

    Evidence iPSC differentiation, conditional Eif4a3 mouse knockout, cell migration and differentiation assays

    PMID:28334780

    Open questions at the time
    • Which eIF4A3-dependent mRNA targets drive NCC migration defects unknown
    • Relative contribution of EJC-dependent NMD vs. other eIF4A3 functions in NCCs unresolved
  13. 2019 High

    Identification of CDK1/2-mediated phosphorylation of T163 revealed cell cycle–dependent regulation of EJC deposition: phosphorylation shifts eIF4A3 from RNA/EJC binding toward CWC22 association, modulating NMD fidelity across the cell cycle.

    Evidence Mass spectrometry, in vitro kinase assay, phosphomutant analysis, Co-IP, NMD reporter, cell cycle synchronization

    PMID:30784594

    Open questions at the time
    • Phosphatase that reverses T163 phosphorylation unidentified
    • Whether other post-translational modifications regulate eIF4A3 unknown
  14. 2021 High

    Demonstration that eIF4A3 resides in the nucleolar small subunit processome and resolves R-loops for rRNA processing provided the mechanistic basis for the previously identified ribosome biogenesis role, linking eIF4A3 depletion to p53-dependent cell cycle arrest via the RiBi checkpoint.

    Evidence Nucleolar fractionation, R-loop detection, multi-omics (proteomics, translatome, transcriptome), siRNA knockdown

    PMID:34348895

    Open questions at the time
    • Direct R-loop unwinding by eIF4AIII not reconstituted in vitro with purified components
    • Whether NOM1 participates in R-loop resolution unknown
  15. 2021 Medium

    Discovery that eIF4A3 depletion causes TFEB nuclear translocation and enhanced autophagic flux revealed an unexpected role in autophagy suppression through cytoplasmic retention of a master autophagy transcription factor.

    Evidence RNAi knockdown, TFEB subcellular fractionation, autophagic flux assays

    PMID:34643458

    Open questions at the time
    • Whether eIF4A3 directly interacts with TFEB or acts indirectly (e.g., through mTOR signaling or NMD targets) not established
    • Mechanism of TFEB cytoplasmic retention by eIF4A3 unresolved
    • Not independently confirmed by another lab
  16. 2023 High

    Identification of a direct eIF4A3–eIF3g interaction that drives internal ribosome entry on circular RNAs established a new translation initiation mechanism linking EJC-deposited eIF4A3 on circRNAs to eIF3-mediated ribosome recruitment.

    Evidence Co-IP, pulldown, in vitro circRNA translation, polysome profiling, transcriptome-wide ribosome association

    PMID:37811880

    Open questions at the time
    • Structural basis of eIF4A3–eIF3g interaction unknown
    • Whether eIF4A3 helicase activity is required for circRNA translation not tested
    • Scope of endogenous circRNAs translated via this mechanism not fully mapped
  17. 2024 High

    Demonstration that eIF4A3 directly binds and polymerizes microtubules—mutually exclusive of EJC binding—to promote axon growth revealed a fundamentally RNA-independent cytoskeletal function, expanding eIF4A3's biology beyond nucleic acid metabolism.

    Evidence In vitro microtubule binding and polymerization reconstitution, competition with EJC, live imaging, rescue in cortical organoids

    PMID:39182224

    Open questions at the time
    • Structural determinants of microtubule binding on eIF4A3 surface not mapped
    • Whether this function operates outside neurons unknown
    • How the switch between EJC-bound and microtubule-bound pools is regulated in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanisms governing the partitioning of eIF4A3 among its distinct functional pools—EJC assembly, ribosome biogenesis, circRNA translation, TFEB regulation, and microtubule binding—and how these are coordinately regulated remain unresolved.
  • No unified model for how eIF4A3 is allocated among competing functions
  • Phosphatase(s) opposing CDK1/2-mediated T163 phosphorylation unidentified
  • Direct R-loop helicase activity not reconstituted with purified eIF4A3

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140657 ATP-dependent activity 3 GO:0140098 catalytic activity, acting on RNA 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1
Partners
CASC3CTIFCWC22EIF3GMAGOHNOM1RBM8A
Complex memberships
Exon junction complex (EJC)Small subunit processome

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 eIF4AIII exhibits RNA-dependent ATPase activity and ATP-dependent RNA helicase activity but, unlike eIF4AI, fails to substitute for eIF4AI in an in vitro-reconstituted 40S ribosome binding assay and instead inhibits translation in a reticulocyte lysate system. Additionally, whereas eIF4AI binds independently to both the middle and carboxy-terminal fragments of eIF4G, eIF4AIII binds only to the middle fragment. In vitro biochemical assays (ATPase assay, RNA helicase assay, 40S ribosome binding reconstitution, reticulocyte lysate translation, eIF4G fragment binding) Molecular and cellular biology High 10523622
2004 eIF4AIII is a core component of the exon junction complex (EJC), crosslinking and antibody inhibition studies indicate it constitutes at least part of the RNA-binding platform anchoring other EJC components to spliced mRNAs, and it is essential for nonsense-mediated mRNA decay (NMD) in mammalian cells. eIF4AIII associates in vitro and in vivo with Y14 and Magoh. Crosslinking, antibody inhibition, Co-IP, siRNA knockdown with NMD reporter assay Nature structural & molecular biology High 14973490 15024115 15034551
2004 In Drosophila, eIF4AIII interacts with Barentsz and the Mago-Y14 heterodimer, providing a molecular link between Barentsz and the heterodimer within the oskar mRNA localization RNP complex. Both Barentsz and eIF4AIII are essential for NMD in human cells. Co-immunoprecipitation, genetic knockdown, NMD assay Nature High 14973490
2004 eIF4AIII is specifically recruited to the EJC during pre-mRNA splicing in the nucleus (not eIF4AI), and siRNA against eIF4AIII but not eIF4AI/II inhibits NMD, suggesting eIF4AIII acts as a nuclear translation-like factor that substitutes for eIF4AI/II during NMD. siRNA knockdown, NMD reporter assay, nuclear fractionation, splicing assay Proceedings of the National Academy of Sciences of the United States of America High 15024115
2005 Recombinant EJC core subunits MLN51, MAGOH, Y14, and eIF4AIII bound to ATP are necessary and sufficient to form a highly stable complex on single-stranded RNA. The stable RNA association is maintained by inhibition of eIF4AIII ATPase activity by the MAGOH-Y14 heterodimer, locking the EJC core onto RNA. In vitro reconstitution with recombinant proteins, crosslinking, RNase protection, ATPase assay Nature structural & molecular biology High 16170325
2006 Mutational analysis of human eIF4AIII revealed that helicase motifs Ia and VI, and one eIF4AIII-specific region, are crucial for EJC formation and NMD activation. An additional eIF4AIII-specific motif forms part of the MLN51 binding site. Importantly, mutations in Walker A and B motifs that eliminate RNA-dependent ATP hydrolysis in vitro do not impair EJC formation or NMD. Site-specific mutagenesis, in vitro and in vivo EJC formation assays, NMD rescue experiments after RNAi depletion RNA (New York, N.Y.) High 16495234
2007 MLN51 stimulates the RNA-helicase activity of eIF4AIII by decreasing KM for ATP by an order of magnitude and increasing kcat 30-fold. The ATP-bound form of the eIF4AIII-MLN51 complex has 100-fold higher affinity for RNA than the unbound form; ATP hydrolysis reduces this affinity. MAGOH-Y14 inhibit MLN51-stimulated ATPase activity but not back to background levels. In vitro ATPase assay, RNA helicase assay, kinetic analysis PloS one High 17375189
2007 Immunodepletion of eIF4AIII from HeLa nuclear extract showed it is dispensable for pre-mRNA splicing in vitro but is required for the splicing-dependent loading of the Y14/Magoh heterodimer onto mRNA. EJC assembly onto mRNA occurs at late stages of the splicing reaction and requires HRH1/hPrp22. Immunodepletion from nuclear extract, in vitro splicing assay, Western blot Proceedings of the National Academy of Sciences of the United States of America High 17606899
2011 Human eIF4AIII interacts with NOM1, an eIF4G-like protein, in vitro and in vivo. Knockdown of eIF4AIII and NOM1 demonstrated this novel conserved complex acts in pre-rRNA processing. Furthermore, human eIF4AIII functionally complements the lethal phenotype and 18S rRNA biogenesis defect of fal1Δ yeast, establishing functional orthology. Yeast complementation, Co-IP, pulldown, RNAi knockdown with rRNA processing assay Genes & development High 21576267
2011 eIF4A3 binds SECIS elements from non-essential selenoproteins during selenium deficiency to repress selenoprotein translation. A two-site interaction model was identified where eIF4A3 binds the internal and apical loops of the SECIS element; uridine in the SECIS core is required for complex stability. Both globular domains of eIF4A3, connected by a linker, are critical for SECIS binding. RNA gel shift, surface plasmon resonance, enzymatic footprinting, domain mapping Nucleic acids research High 21685449
2012 CWC22 directly contacts eIF4AIII and prevents it from binding RNA. In vitro splicing assays revealed CWC22 introduces eIF4AIII to spliceosomes before remodeling to facilitate eIF4AIII incorporation into the EJC. CWC22 knockdown abolished EJC assembly in vivo. Recombinant protein pulldown, in vitro splicing assay, RNAi knockdown, EJC assembly assay Nature structural & molecular biology High 22961380
2013 Crystal structure of human eIF4AIII in complex with the MIF4G domain of CWC22 at 2.0-Å resolution shows that CWC22 MIF4G binds both RecA domains of eIF4AIII. In the complex, RNA-binding and ATP-binding motifs of the two RecA domains are in diametrically opposite positions rather than facing each other as required for the active state, revealing the mechanism of eIF4AIII inhibition by an MIF4G domain. X-ray crystallography at 2.0-Å resolution with functional validation Proceedings of the National Academy of Sciences of the United States of America High 24218557
2013 An expansion of 18- or 20-nucleotide repeat motifs in the 5' UTR of EIF4A3 causes Richieri-Costa-Pereira syndrome (RCPS). EIF4A3 transcript abundance is reduced in affected individuals, and a missense substitution affecting eIF4AIII interaction with UPF3B was found in an atypical patient. Zebrafish eif4a3 knockdown causes underdevelopment of craniofacial cartilage and bone. Identity-by-descent mapping, sequencing, qRT-PCR in patient cells, zebrafish morpholino knockdown American journal of human genetics High 24360810
2014 eIF4AIII is recruited to the 5'-end of CBC-bound mRNAs via direct interaction with CTIF (CBC-dependent translation initiation factor), independent of splicing/EJC deposition. This recruitment promotes efficient unwinding of secondary structures in the 5'UTR and enhances CBC-dependent translation, demonstrated by polysome fractionation, tethering experiments, and in vitro reconstitution with recombinant proteins. Polysome fractionation, tethering assay, in vitro reconstitution with recombinant proteins, Co-IP Proceedings of the National Academy of Sciences of the United States of America High 25313076
2015 CWC22 mediates both pre-mRNA splicing and EJC assembly. An eIF4A3-binding deficient mutant of CWC22 uncouples the two functions, abolishing EJC assembly without affecting splicing. High-throughput RNA-sequencing of CWC22-depleted cells identified global pre-mRNA splicing defects. Mutagenesis of CWC22, RNA-seq, EJC assembly assay, splicing assay Nucleic acids research High 25870412
2017 Neural crest cell (NCC) defects explain RCPS craniofacial abnormalities caused by EIF4A3 loss-of-function. RCPS iPSC-derived NCCs have decreased migratory capacity, Eif4a3 haploinsufficient mice exhibit altered mandibular process fusion and micrognathia, and NCC-specific Eif4a3 haploinsufficiency recapitulates the phenotype. NCC-derived mesenchymal stem-like cells showed premature bone differentiation and compromised chondrogenesis. Patient-derived iPSC differentiation, conditional mouse knockout, live cell migration assay, differentiation assays Human molecular genetics High 28334780
2017 Small-molecule 1,4-diacylpiperazine derivatives were identified as selective eIF4A3 inhibitors that bind eIF4A3 at a non-ATP binding allosteric site (confirmed by SPR), inhibit NMD in cells, and are selective over other helicases including eIF4AI/II. High-throughput screening, chemical optimization, surface plasmon resonance, NMD reporter assay Journal of medicinal chemistry High 28358513
2017 ATP-competitive eIF4A3 inhibitors with submicromolar ATPase inhibitory activity and excellent selectivity over other helicases were discovered, providing chemical probes for eIF4A3 ATPase function. ATPase inhibition assay, selectivity profiling Bioorganic & medicinal chemistry Medium 28283335
2019 Threonine 163 (T163) within the RNA-binding motif of eIF4A3 is phosphorylated by CDK1 and CDK2 in a cell cycle-dependent manner. T163 phosphorylation hinders eIF4A3 binding to spliced mRNAs and other EJC components while promoting its association with CWC22, which guides eIF4A3 to active spliceosomes. This affects the fidelity of EJC deposition and consequently NMD efficiency. Mass spectrometry, phosphorylation assay with CDK1/2, Co-IP, RNA binding assay, NMD reporter assay, cell cycle synchronization Cell reports High 30784594
2019 Pharmacological inhibition of eIF4A3 using allosteric small-molecule inhibitors revealed conserved roles in cell cycle control. EIF4A3-dependent splicing reactions have a distinct genome-wide pattern of associated RNA-binding protein motifs. EIF4A3 inhibition suppresses stress granule induction and maintenance, in part through regulation of G3BP1 and TIA1 scaffold protein expression. Graded small-molecule inhibition, transcriptome-wide RNA-seq, stress granule imaging, Western blot Communications biology High 31069274
2019 eIF4A3 promotes avian influenza A virus replication by interacting with viral PB2, PB1, and NP proteins. eIF4A3 is essential for viral RNA polymerase activity, viral RNA synthesis, and specifically for splicing of viral intron-containing mRNAs (M2 and NS2) and their nuclear export. Co-immunoprecipitation with viral proteins, siRNA depletion, viral RNA analysis, nuclear-cytoplasmic fractionation Frontiers in microbiology Medium 31379779
2021 eIF4A3 resides in nucleoli within the small subunit processome and regulates rRNA processing via R-loop clearance. EIF4A3 depletion induces cell cycle arrest through impaired ribosome biogenesis (RiBi) checkpoint-mediated p53 induction and reprogrammed translation of cell cycle regulators, including alternative MDM2 transcript isoforms that control p53. Nucleolar fractionation, R-loop detection, multilevel omics (proteomics, translatome, transcriptome), siRNA knockdown Science advances High 34348895
2021 EIF4A3 acts as a negative regulator of macroautophagy by maintaining low basal autophagy levels through the cytosolic retention of the transcription factor TFEB. EIF4A3 depletion causes TFEB nuclear translocation, inducing a transcriptional response that induces both early and late autophagy steps and enhances autophagic flux. RNAi knockdown, TFEB nuclear-cytoplasmic fractionation, autophagic flux assays Autophagy Medium 34643458
2021 EIF4A3 promotes mRNA nuclear export: circ_0004296 inhibits PCa metastasis by binding EIF4A3 and promoting its retention in the nucleus, which prevents ETS1 mRNA nuclear export and downregulates ETS1 expression. EIF4A3 silencing alone suppressed PCa cell proliferation, migration, and invasion. RNA pull-down, mass spectrometry, RIP, nuclear-cytoplasmic RNA fractionation, siRNA knockdown Journal of experimental & clinical cancer research Medium 34696782
2022 eIF4A3 controls neural crest cell-autonomous cortical progenitor mitosis duration, which influences progeny cell fate and viability. Eif4a3 haploinsufficiency causes cell death and impaired neurogenesis; p53 accounts for apoptosis but additional p53-independent mechanisms contribute to later neurogenesis defects. Phenotypes are conserved in cortical organoids from RCPS iPSCs. EIF4A3 controls neuron generation via the EJC. Eif4a3;p53 compound mouse models, live imaging of mitosis, cortical organoids from RCPS iPSCs, rescue experiments Development (Cambridge, England) High 37139782
2022 eIF4A3 is essential for maintenance of embryonic stem cell pluripotency via post-transcriptional control of the cell cycle. Specifically, eIF4A3 is required for efficient nuclear export of Ccnb1 (Cyclin B1) mRNA, and its depletion causes loss of pluripotency through cell cycle dysregulation. RNAi screen, siRNA knockdown, nuclear export assay (mRNA fractionation), pluripotency assays Nucleic acids research Medium 36416264
2022 eIF4A3 acts as an oncogene in HCC by modulating FGFR4 splicing. EIF4A3 silencing blocked the cellular response to the FGFR4 natural ligand FGF19, and restoration of non-spliced FGFR4 full-length version blunted the effects of EIF4A3 silencing. EIF4A3 siRNA knockdown in hepatocellular carcinoma cell lines, splicing analysis, FGFR4 rescue experiments, xenograft model Clinical and translational medicine Medium 36419260
2023 eIF4A3 directly interacts with eIF3g (a subunit of the eIF3 complex), and this direct interaction serves as a molecular linker between eIF4A3 and the eIF3 complex to facilitate internal ribosomal entry and translation of circular RNAs. In vitro-synthesized circRNA demonstrates eIF4A3-driven internal translation dependent on eIF4A3-eIF3g interaction. Transcriptome-wide analysis shows efficient polysomal association of endogenous circRNAs requires eIF4A3. Co-IP, pulldown, in vitro circRNA translation assay, polysome profiling, transcriptome-wide ribosome association analysis Nucleic acids research High 37811880
2024 EIF4A3 directly binds microtubules, mutually exclusive of EJC binding, and promotes microtubule polymerization in vitro. In vitro reconstitution and rescue experiments demonstrated that EIF4A3-microtubule association is a major contributor to axon growth, revealing an RNA-independent cytoskeletal function of EIF4A3 in neurons. Biochemical microtubule binding assay, in vitro polymerization reconstitution, competition experiments, live imaging of microtubule dynamics, rescue experiments in cortical organoids Cell reports High 39182224
2016 eIF4AIII RNA helicase is required for efficient human cytomegalovirus (HCMV) replication. Depletion of eIF4AIII limited viral DNA accumulation, export of viral mRNAs from the nucleus, and production of progeny virus, while being dispensable for viral transcript ribosome association. siRNA depletion, viral replication assay, nuclear mRNA export assay, ribosome association analysis Virology Medium 26773380
2012 Eif4a3 knockdown in Xenopus laevis causes full-body paralysis; mechanistically, ryr (ryanodine receptor) transcripts are incorrectly spliced in Eif4a3 morphants, and inhibition of Ryr function similarly results in embryonic paralysis, demonstrating that EJC mediates muscle function via pre-mRNA splicing regulation. Morpholino knockdown in Xenopus, calcium imaging of muscle cells, splicing analysis by RT-PCR Developmental biology Medium 22944195
2010 Knockdown of Eif4a3 in Xenopus laevis embryos results in full-body paralysis with defects in sensory neuron, pigment cell, and cardiac development, establishing an essential role for the EJC core component Eif4a3 in vertebrate embryogenesis and neural plate border derivative development. Morpholino knockdown in Xenopus laevis, phenotypic analysis Developmental dynamics Medium 20549732
2024 EIF4A3 is identified as a regulator of circDdb1 expression in muscle atrophy. EIF4A3-induced circDdb1 encodes a novel protein, circDdb1-867aa, which binds eEF2 and increases its phosphorylation at Thr56 to reduce protein translation and promote muscle atrophy. RIP, RNA pulldown, Co-IP, phosphorylation assay, in vivo mouse models, in vitro translation assay Advanced science Medium 39412095

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer. Molecular cancer 345 32264877
2014 A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. Cancer cell 341 25203321
2004 An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 303 14973490
2005 The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nature structural & molecular biology 274 16170325
2004 eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nature structural & molecular biology 214 15034551
2018 LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. Life sciences 182 29421439
2022 EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling. Cancer research 174 34965937
2021 EIF4A3-induced circular RNA ASAP1 promotes tumorigenesis and temozolomide resistance of glioblastoma via NRAS/MEK1/ERK1-2 signaling. Neuro-oncology 168 32926734
2004 A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay. Proceedings of the National Academy of Sciences of the United States of America 154 15024115
1999 Eukaryotic translation initiation factor 4AIII (eIF4AIII) is functionally distinct from eIF4AI and eIF4AII. Molecular and cellular biology 123 10523622
2021 Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3. Theranostics 96 33859754
2012 Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. Nature structural & molecular biology 96 22961380
2013 A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a craniofacial disorder associated with limb defects. American journal of human genetics 93 24360810
2021 hsa_circ_0068631 promotes breast cancer progression through c-Myc by binding to EIF4A3. Molecular therapy. Nucleic acids 82 34513299
2009 Dynamic behavior of Arabidopsis eIF4A-III, putative core protein of exon junction complex: fast relocation to nucleolus and splicing speckles under hypoxia. The Plant cell 77 19435936
2022 EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression. Journal of experimental & clinical cancer research : CR 70 35513835
2020 Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3-mediated E2F1 activation. Clinical and translational medicine 66 33252856
2006 Mutational analysis of human eIF4AIII identifies regions necessary for exon junction complex formation and nonsense-mediated mRNA decay. RNA (New York, N.Y.) 62 16495234
2014 eIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in 5'UTR. Proceedings of the National Academy of Sciences of the United States of America 61 25313076
2023 Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205. Cell death discovery 57 37160894
2021 EIF4A3-induced circ_0084615 contributes to the progression of colorectal cancer via miR-599/ONECUT2 pathway. Journal of experimental & clinical cancer research : CR 57 34253241
2021 The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output. Science advances 56 34348895
2007 Splicing remodels messenger ribonucleoprotein architecture via eIF4A3-dependent and -independent recruitment of exon junction complex components. Proceedings of the National Academy of Sciences of the United States of America 53 17606899
2011 Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes & development 52 21576267
2017 Long Noncoding RNA FAL1 Promotes Cell Proliferation, Invasion and Epithelial-Mesenchymal Transition Through the PTEN/AKT Signaling Axis in Non-Small Cell Lung Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 50 28854421
2020 Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes. The EPMA journal 49 32549918
2018 Long non-coding RNA FAL1 functions as a ceRNA to antagonize the effect of miR-637 on the down-regulation of AKT1 in Hirschsprung's disease. Cell proliferation 48 30062828
2019 LINC00680 and TTN-AS1 Stabilized by EIF4A3 Promoted Malignant Biological Behaviors of Glioblastoma Cells. Molecular therapy. Nucleic acids 47 32000032
2016 Relationship of Focally Amplified Long Noncoding on Chromosome 1 (FAL1) lncRNA with E2F Transcription Factors in Thyroid Cancer. Medicine 47 26825907
2022 EIF4A3-induced circTOLLIP promotes the progression of hepatocellular carcinoma via the miR-516a-5p/PBX3/EMT pathway. Journal of experimental & clinical cancer research : CR 45 35509064
2013 Crystal structure of the human eIF4AIII-CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain. Proceedings of the National Academy of Sciences of the United States of America 45 24218557
2007 MLN51 stimulates the RNA-helicase activity of eIF4AIII. PloS one 44 17375189
2014 The expanding functions of cellular helicases: the tombusvirus RNA replication enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box RNA helicases to promote viral asymmetric RNA replication. PLoS pathogens 43 24743583
2023 CAF-derived exosomal lncRNA FAL1 promotes chemoresistance to oxaliplatin by regulating autophagy in colorectal cancer. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 39 37400281
2021 Hsa_circ_0004296 inhibits metastasis of prostate cancer by interacting with EIF4A3 to prevent nuclear export of ETS1 mRNA. Journal of experimental & clinical cancer research : CR 39 34696782
2019 eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle. Cell reports 39 30784594
2017 EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome. Human molecular genetics 39 28334780
2023 EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway. Biomarker research 38 37280654
2020 LINC00667 promotes the proliferation, migration, and pathological angiogenesis in non-small cell lung cancer through stabilizing VEGFA by EIF4A3. Cell biology international 38 32281700
2022 EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway. Cell death discovery 37 35236829
2024 EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cisplatin resistance. Journal of experimental & clinical cancer research : CR 36 38163881
2023 EIF4A3-induced circZFAND6 promotes breast cancer proliferation and metastasis through the miR-647/FASN axis. Life sciences 36 37127184
2018 LncRNA FAL1 promotes carcinogenesis by regulation of miR-637/NUPR1 pathway in colorectal cancer. The international journal of biochemistry & cell biology 36 30267804
2021 EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression. Cell death & disease 35 34716310
2022 CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3. Experimental cell research 34 35752345
2021 Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling. International journal of molecular sciences 34 33924522
2021 YY1 and eIF4A3 are mediators of the cell proliferation, migration and invasion in cholangiocarcinoma promoted by circ-ZNF609 by targeting miR-432-5p to regulate LRRC1. Aging 33 34898474
2022 LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability. Cellular & molecular biology letters 32 36221055
2019 Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation. Communications biology 32 31069274
2023 EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression. Cell death & disease 30 37626035
2021 circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3. Analytical cellular pathology (Amsterdam) 30 34660182
2015 CWC22-dependent pre-mRNA splicing and eIF4A3 binding enables global deposition of exon junction complexes. Nucleic acids research 29 25870412
2024 Circular RNA hsa_circ_0000467 promotes colorectal cancer progression by promoting eIF4A3-mediated c-Myc translation. Molecular cancer 28 39085875
2017 Discovery of Novel 1,4-Diacylpiperazines as Selective and Cell-Active eIF4A3 Inhibitors. Journal of medicinal chemistry 27 28358513
2017 Discovery of selective ATP-competitive eIF4A3 inhibitors. Bioorganic & medicinal chemistry 26 28283335
2023 An interaction between eIF4A3 and eIF3g drives the internal initiation of translation. Nucleic acids research 25 37811880
2021 CircETFA upregulates CCL5 by sponging miR-612 and recruiting EIF4A3 to promote hepatocellular carcinoma. Cell death discovery 25 34716323
2020 Circ_cse1l Inhibits Colorectal Cancer Proliferation by Binding to eIF4A3. Medical science monitor : international medical journal of experimental and clinical research 25 32857753
2023 EIF4A3-Induced Exosomal circLRRC8A Alleviates Granulosa Cells Senescence Via the miR-125a-3p/NFE2L1 axis. Stem cell reviews and reports 24 37243831
2022 N6-Methyladenosine Modification of CIRCKRT17 Initiated by METTL3 Promotes Osimertinib Resistance of Lung Adenocarcinoma by EIF4A3 to Enhance YAP1 Stability. Cancers 24 36428672
2023 Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis. Clinical and experimental hypertension (New York, N.Y. : 1993) 22 36890708
2019 Avian Influenza A Virus Polymerase Recruits Cellular RNA Helicase eIF4A3 to Promote Viral mRNA Splicing and Spliced mRNA Nuclear Export. Frontiers in microbiology 22 31379779
2010 Regulation of vertebrate embryogenesis by the exon junction complex core component Eif4a3. Developmental dynamics : an official publication of the American Association of Anatomists 22 20549732
2024 Hypoxia-enhanced YAP1-EIF4A3 interaction drives circ_0007386 circularization by competing with CRIM1 pre-mRNA linear splicing and promotes non-small cell lung cancer progression. Journal of experimental & clinical cancer research : CR 21 39030638
2023 CircKIF4A combines EIF4A3 to stabilize SDC1 expression to activate c-src/FAK and promotes TNBC progression. Cellular signalling 21 37121557
2023 EIF4a3-regulated circRABL2B regulates cell stemness and drug sensitivity of lung cancer via YBX1-dependent downregulation of MUC5AC expression. International journal of biological sciences 21 37324942
2022 EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma. Cellular and molecular life sciences : CMLS 21 35680727
2021 EIF4A3: a gatekeeper of autophagy. Autophagy 21 34643458
2022 Spliceosomal profiling identifies EIF4A3 as a novel oncogene in hepatocellular carcinoma acting through the modulation of FGFR4 splicing. Clinical and translational medicine 20 36419260
2018 Long noncoding RNA FAL1 promotes proliferation and inhibits apoptosis of human colon cancer cells. IUBMB life 20 30290064
2016 The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication. Virology 20 26773380
2015 Oncogenic long noncoding RNA FAL1 in human cancer. Molecular & cellular oncology 20 27308441
2016 The RNA Polymerase II C-Terminal Domain Phosphatase-Like Protein FIERY2/CPL1 Interacts with eIF4AIII and Is Essential for Nonsense-Mediated mRNA Decay in Arabidopsis. The Plant cell 19 26887918
2011 Identification of a signature motif for the eIF4a3-SECIS interaction. Nucleic acids research 19 21685449
2022 EIF4A3-induced circCCNB1 (hsa_circ_0001495) promotes glioma progression by elevating CCND1 through interacting miR-516b-5p and HuR. Metabolic brain disease 18 35038081
2020 lncRNA HOXC-AS1 promotes gastric cancer via binding eIF4AIII by activating Wnt/β-catenin signaling. The journal of gene medicine 18 32307743
2024 EIF4A3-Induced Circular RNA CircDdb1 Promotes Muscle Atrophy through Encoding a Novel Protein CircDdb1-867aa. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39412095
2023 Exosomal circCOL1A1 promotes angiogenesis via recruiting EIF4A3 protein and activating Smad2/3 pathway in colorectal cancer. Molecular medicine (Cambridge, Mass.) 17 37940881
2025 EIF4A3-Mediated Biogenesis of CircFADS1 Promotes the Progression of Hepatocellular Carcinoma via Wnt/β-Catenin Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 39965082
2023 EIF4A3 induced circABCA5 promotes the gastric cancer progression by SPI1 mediated IL6/JAK2/STAT3 signaling. American journal of cancer research 16 36895988
2023 EIF4A3-induced circular RNA SCAP facilitates tumorigenesis and progression of non-small-cell lung cancer via miR-7/SMAD2 signaling. Environmental science and pollution research international 16 37079240
2019 LncRNA FAL1 promotes the development of oral squamous cell carcinoma through regulating the microRNA-761/CRKL pathway. European review for medical and pharmacological sciences 16 31298329
2022 EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling. BMC cancer 15 36443711
2009 Localization of eIF4A-III in the nucleolus and splicing speckles is an indicator of plant stress. Plant signaling & behavior 15 20514231
2023 The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis. Development (Cambridge, England) 14 37139782
2023 Extracellular vesicular lncRNA FAL1 promotes hepatocellular carcinoma cell proliferation and invasion by inducing macrophage M2 polarization. Journal of physiology and biochemistry 14 37147492
2022 eIF4A3-induced circWAC promotes breast cancer progression through mediating miR-599/E2F3 axis. The Kaohsiung journal of medical sciences 14 34989110
2022 An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity. Nucleic acids research 14 36416264
2012 Eif4a3 is required for accurate splicing of the Xenopus laevis ryanodine receptor pre-mRNA. Developmental biology 14 22944195
2023 Circ-AMOTL1 enhances cardiac fibrosis through binding with EIF4A3 and stabilizing MARCKS expression in diabetic cardiomyopathy. Cellular signalling 13 37586467
2021 The EIF4A3/CASC2/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas. Frontiers in oncology 13 34408982
2021 EIF4A3-mediated hsa_circ_0088088 promotes the carcinogenesis of breast cancer by sponging miR-135-5p. Journal of biochemical and molecular toxicology 13 34463003
2020 Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway. European review for medical and pharmacological sciences 13 31957817
2019 FAL1: A critical oncogenic long non-coding RNA in human cancers. Life sciences 13 31610208
2024 The RNA-binding protein EIF4A3 promotes axon development by direct control of the cytoskeleton. Cell reports 12 39182224
2023 EIF4A3 Acts on the PI3K-AKT-ERK1/2-P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma. Molecular cancer research : MCR 12 37011005
2022 Plasmacytoma variant translocation 1 stabilized by EIF4A3 promoted malignant biological behaviors of lung adenocarcinoma by generating circular RNA LMNB2. Bioengineered 12 35435126
2022 EIF4A3 stabilizes the expression of lncRNA AGAP2-AS1 to activate cancer-associated fibroblasts via MyD88/NF-κb signaling. Thoracic cancer 12 36541122
2021 Circ_0074027 binds to EIF4A3 and promotes gastric cancer progression. Oncology letters 12 34457059
2017 Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors. ACS medicinal chemistry letters 11 29057054