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Showing EIF4A3 — FAL1 is a alias.

EIF4A3

Eukaryotic initiation factor 4A-III · UniProt P38919

Length
411 aa
Mass
46.9 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF4A3 is a nuclear DEAD-box ATP-dependent RNA helicase that serves as the catalytic, RNA-clamping core of the exon junction complex (EJC), distinguishing it functionally from cytoplasmic eIF4AI/II (PMID:14730019, PMID:10523622). Recruited to the active spliceosome at late stages of splicing by the direct binding partner CWC22, it is deposited onto spliced mRNAs and anchors the MAGOH-Y14 heterodimer and MLN51 (PMID:17606899, PMID:22961380, PMID:25870412, PMID:14730019). Its enzymatic cycle is tightly regulated: MLN51 stimulates ATP-dependent RNA binding while MAGOH-Y14 inhibit ATPase activity to lock the complex stably onto RNA, and CWC22 holds the two RecA domains in an inactive conformation that prevents premature RNA engagement (PMID:16170325, PMID:17375189, PMID:24218557). Through this EJC platform, EIF4A3 is essential for nonsense-mediated mRNA decay, mRNA localization, nuclear mRNA export, and translational enhancement of spliced and cap-binding-complex-bound mRNAs via CTIF (PMID:15034551, PMID:14973490, PMID:15024115, PMID:25313076). EJC loading is gated across the cell cycle by CDK1/2 phosphorylation of T163, which shifts EIF4A3 from mRNA/EJC association toward CWC22-guided spliceosome targeting (PMID:30784594). Beyond the canonical EJC, EIF4A3 functions in nucleolar pre-rRNA processing with the eIF4G-like partner NOM1 and via R-loop clearance, coupling ribosome biogenesis to a p53-dependent checkpoint (PMID:21576267, PMID:34348895). It governs developmental and homeostatic programs through splicing control—maintaining autophagy by ensuring correct GSK3B splicing and thereby TFEB regulation, and supporting neural crest and cortical progenitor development (PMID:34158631, PMID:28334780, PMID:37139782). In humans, an expansion of repeat motifs in the EIF4A3 5' UTR reduces transcript levels and causes Richieri-Costa-Pereira syndrome, an acrofacial dysostosis modeled by craniofacial defects upon loss of function in zebrafish, mice, and patient iPSCs (PMID:24360810, PMID:28334780). Most unexpectedly, EIF4A3 directly binds and polymerizes microtubules in a manner mutually exclusive with EJC assembly to promote axon growth (PMID:39182224).

Mechanistic history

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

    Established that human eIF4AIII is a biochemically active ATP-dependent RNA helicase distinct from translation-initiation eIF4AI/II, raising the question of what non-canonical role it serves.

    Evidence In vitro ATPase, RNA helicase, 40S ribosome binding, and reticulocyte translation assays with eIF4G fragment pulldowns

    PMID:10523622

    Open questions at the time
    • Did not identify the in vivo complex or RNA substrate
    • Functional role distinct from translation left unexplained
  2. 2004 High

    Resolved that eIF4A3 is the nuclear RNA-binding core of the EJC and is essential for NMD, defining its primary cellular function.

    Evidence Co-IP, in vitro splicing and footprint mapping, subcellular fractionation, crosslinking, and siRNA NMD reporter assays across mammalian and Drosophila systems

    PMID:14730019 PMID:14973490 PMID:15024115 PMID:15034551

    Open questions at the time
    • Mechanism of recruitment to spliceosome unknown
    • How RNA clamping is stabilized not yet defined
  3. 2005 High

    Defined the minimal stable EJC and showed that EIF4A3 ATPase regulation by partner subunits underlies stable RNA clamping.

    Evidence Recombinant reconstitution with MLN51/MAGOH/Y14, crosslinking, RNase protection, and ATPase assays

    PMID:16170325

    Open questions at the time
    • Did not establish how EIF4A3 is delivered to the spliceosome in vivo
    • Structural basis of inhibition not resolved
  4. 2007 High

    Quantified the helicase regulatory logic—MLN51 stimulation and MAGOH-Y14 inhibition of ATPase/RNA-affinity—and showed EIF4A3 is required for splicing-dependent EJC loading but dispensable for splicing itself.

    Evidence ATPase kinetics and RNA-binding with recombinant proteins; immunodepletion plus in vitro splicing/EJC assembly assays

    PMID:17375189 PMID:17606899

    Open questions at the time
    • Factor escorting EIF4A3 to spliceosome not identified
    • Timing relative to splicing steps incompletely mapped
  5. 2011 High

    Extended EIF4A3 function beyond the EJC into nucleolar pre-rRNA processing through a conserved eIF4A/eIF4G-like module with NOM1.

    Evidence Yeast complementation, genetic suppressor screen, reciprocal Co-IP, and siRNA with rRNA processing readout

    PMID:21576267

    Open questions at the time
    • Helicase substrate in rRNA processing not defined
    • Relationship to EJC pool unclear
  6. 2011 High

    Identified a transcript-selective translational repressor role through direct SECIS-element binding during selenium deficiency.

    Evidence RNA gel shifts, SPR, enzymatic footprinting, domain truncation

    PMID:21685449

    Open questions at the time
    • Cellular regulation of this switch not detailed
    • Relationship to EJC-bound pool unknown
  7. 2012 High

    Identified CWC22 as the direct factor that escorts EIF4A3 to spliceosomes and prevents premature RNA binding, answering how EIF4A3 is targeted for EJC deposition.

    Evidence Recombinant direct binding, in vitro splicing, RNAi, Co-IP, mass spectrometry; replicated by independent lab

    PMID:22961380 PMID:25870412

    Open questions at the time
    • Structural mechanism of inhibition pending
    • How handoff to EJC partners occurs not resolved
  8. 2013 High

    Provided the atomic basis for CWC22-mediated inhibition by showing it holds both RecA domains in inactive positions, and established EIF4A3 as the causative gene for Richieri-Costa-Pereira syndrome.

    Evidence 2.0 Å crystal structure of eIF4AIII-CWC22 MIF4G complex; IBD mapping, sequencing, qRT-PCR, zebrafish morpholino phenotyping

    PMID:24218557 PMID:24360810

    Open questions at the time
    • Cell type underlying RCPS not yet defined
    • How reduced transcript levels produce specific craniofacial phenotype unresolved
  9. 2014 High

    Demonstrated an EJC-independent translational enhancement role via CTIF recruitment to cap-binding-complex mRNAs, broadening EIF4A3's function to 5' UTR unwinding.

    Evidence Polysome fractionation, tethering, in vitro reconstitution, Co-IP, RNA structure probing

    PMID:25313076

    Open questions at the time
    • Transcript selectivity determinants not defined
    • Quantitative contribution to global translation unknown
  10. 2015 High

    Functionally uncoupled CWC22's splicing and EIF4A3-loading activities, showing global EJC assembly depends on the eIF4A3-CWC22 interaction.

    Evidence CWC22 domain mutagenesis, in vitro splicing, genome-wide RNA-seq, EJC assembly assay

    PMID:25870412

    Open questions at the time
    • Selectivity of EJC deposition across transcripts incompletely explained
  11. 2017 Medium

    Delivered selective chemical probes—both ATP-competitive and allosteric—validating EIF4A3's ATPase and binding sites as druggable.

    Evidence HTS, SPR binding, ATPase inhibition with helicase selectivity panel, cellular NMD reporter

    PMID:28283335 PMID:28358513

    Open questions at the time
    • In vivo efficacy and selectivity not established
    • Single-lab characterization
  12. 2017 High

    Connected nucleolar EIF4A3 to the ribosome biogenesis checkpoint and to neural crest cell-autonomous defects underlying RCPS.

    Evidence Nucleolar fractionation, R-loop detection, multi-omics; patient iPSC-derived NCCs and conditional mouse haploinsufficiency with migration/differentiation assays

    PMID:28334780 PMID:34348895

    Open questions at the time
    • Direct helicase substrate in R-loop clearance unidentified
    • Link between RiBi checkpoint and craniofacial phenotype indirect
  13. 2019 High

    Revealed cell-cycle control of EJC loading through CDK1/2 phosphorylation of T163 that redirects EIF4A3 toward CWC22, and linked EIF4A3 to stress granule regulation.

    Evidence Phospho-site mapping, in vitro kinase assay, Co-IP, NMD reporter, cell-cycle synchronization; small-molecule inhibition with RNA-seq and stress granule imaging

    PMID:30784594 PMID:31069274

    Open questions at the time
    • Phosphatase reversing T163 unknown
    • Stress granule mechanism partly indirect
  14. 2021 High

    Established EIF4A3 as a homeostatic regulator of autophagy via correct GSK3B splicing and downstream TFEB nuclear access.

    Evidence siRNA knockdown, autophagy flux assays, TFEB phosphorylation/localization, GSK3B splicing analysis

    PMID:34158631

    Open questions at the time
    • Whether GSK3B is a direct EJC target unconfirmed
    • Breadth of autophagy-relevant splicing targets unknown
  15. 2022 Medium

    Extended EIF4A3's export and splicing functions to pluripotency maintenance and to oncogenic splicing control in cancer.

    Evidence RNAi screen with ESC pluripotency markers and Ccnb1 export assay; siRNA, xenograft, RNA-seq splicing and FGFR4 rescue in HCC

    PMID:36416264 PMID:36419260

    Open questions at the time
    • Direct vs indirect splicing/export targets not fully separated
    • Single-lab studies
  16. 2023 High

    Uncovered a circRNA translation role through direct EIF4A3-eIF3g interaction driving internal ribosomal entry, and EJC-dependent control of cortical progenitor mitosis.

    Evidence Co-IP, in vitro circRNA translation reconstitution, polysome and transcriptome-wide ribosome profiling; conditional mouse haploinsufficiency, live mitosis imaging, RCPS cortical organoids with EJC rescue

    PMID:37139782 PMID:37811880

    Open questions at the time
    • circRNA selectivity determinants unknown
    • Mechanistic link between EJC and mitotic length not fully defined
  17. 2024 High

    Revealed an EJC-independent, RNA-independent cytoskeletal function in which EIF4A3 directly polymerizes microtubules to drive axon growth, mutually exclusive with EJC assembly.

    Evidence In vitro microtubule reconstitution, competition binding assays, live microtubule imaging in neurons, disease-mutant analysis in cortical organoids

    PMID:39182224

    Open questions at the time
    • Structural basis of microtubule binding unknown
    • Switch between RNA and microtubule pools in cells not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EIF4A3 partitions among its distinct activities—EJC core, nucleolar rRNA processor, SECIS/circRNA translation regulator, and microtubule polymerase—and what governs the choice in a given cell remains unresolved.
  • No unified model of how mutually exclusive functions are regulated
  • Determinants of transcript- and complex-selective engagement unknown
  • Phosphatases and additional post-translational switches uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0045182 translation regulator activity 3 GO:0060090 molecular adaptor activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0140657 ATP-dependent activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005730 nucleolus 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-9612973 Autophagy 1
Partners
CASC3CTIFCWC22EIF3GMAGOHNOM1RBM8A
Complex memberships
exon junction complex (EJC)small subunit (SSU) processome

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 eIF4A3 (EIF4AIII) is a novel core component of the exon junction complex (EJC), associating preferentially with nuclear complexes containing EJC proteins Magoh and Y14, and binding spliced mRNA at the position of the EJC. Unlike eIF4A1/II, eIF4A3 is localized to the nucleus. Co-immunoprecipitation, in vitro splicing and mapping experiments, subcellular fractionation with monoclonal antibodies RNA (New York, N.Y.) High 14730019
2004 eIF4A3 constitutes at least part of the RNA-binding platform anchoring EJC components to spliced mRNAs; it associates in vitro and in vivo with Y14 and Magoh and is essential for nonsense-mediated mRNA decay (NMD) in mammalian cells. Crosslinking, antibody inhibition, Co-IP (in vitro and in vivo), siRNA knockdown with NMD reporter assay Nature structural & molecular biology High 15034551
2004 eIF4A3 (eIF4AIII) is a component of the oskar mRNA localization complex in Drosophila, interacting with Barentsz and the Mago-Y14 heterodimer, thereby providing a molecular link between these proteins. Both Barentsz and eIF4AIII are essential for NMD in human cells. Co-immunoprecipitation, genetic knockdown in Drosophila and human cells, NMD assay Nature High 14973490
2004 siRNA against eIF4AIII (but not eIF4AI/II) inhibits NMD; eIF4AIII is specifically recruited to the EJC during splicing in the nucleus, suggesting it substitutes for eIF4AI/II during NMD. siRNA knockdown, NMD reporter assay, EJC co-purification during splicing Proceedings of the National Academy of Sciences of the United States of America High 15024115
1999 Human eIF4AIII exhibits RNA-dependent ATPase activity and ATP-dependent RNA helicase activity, but fails to substitute for eIF4AI in an in vitro-reconstituted 40S ribosome binding assay and instead inhibits translation in reticulocyte lysate. eIF4AIII binds only the middle fragment of eIF4G (not the C-terminal fragment), unlike eIF4AI. In vitro ATPase assay, RNA helicase assay, reconstituted 40S ribosome binding assay, reticulocyte lysate translation assay, GST pulldown with eIF4G fragments Molecular and cellular biology High 10523622
2005 Recombinant EJC 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 MAGOH-Y14. Recombinant protein reconstitution, crosslinking, RNase protection, ATPase assay Nature structural & molecular biology High 16170325
2006 Motifs Ia and VI (conserved among eIF4A DEAD-box proteins) and one eIF4A3-specific region are crucial for EJC formation and NMD; an additional eIF4A3-specific motif forms part of the MLN51 binding site. Mutations eliminating RNA-dependent ATP hydrolysis in vitro have no detectable consequence for EJC formation or NMD activation. Site-specific mutagenesis, truncation analysis, GFP/GST/Flag fusion localization, in vitro and in vivo protein-protein interaction assays, NMD rescue after RNAi depletion RNA (New York, N.Y.) High 16495234
2007 eIF4A3 is required for the splicing-dependent loading of Y14/Magoh heterodimer onto mRNA but is dispensable for pre-mRNA splicing itself in vitro. EJC assembly onto mRNA occurs at late stages of splicing and requires the second-step splicing/mRNA-release factor HRH1/hPrp22. Immunodepletion of eIF4A3 from HeLa nuclear extract, in vitro splicing assay, EJC assembly assay Proceedings of the National Academy of Sciences of the United States of America High 17606899
2007 MLN51 stimulates the RNA-helicase activity of eIF4AIII by decreasing KM for ATP by ~10-fold and increasing kcat ~30-fold. The ATP-bound form of the eIF4AIII-MLN51 complex has ~100-fold higher RNA affinity than the unbound form; ATP hydrolysis reduces RNA affinity. MAGOH-Y14 inhibit the MLN51-stimulated ATPase activity but not back to background. In vitro ATPase kinetics, RNA-helicase assay, RNA binding assay with recombinant proteins PloS one High 17375189
2011 Human eIF4A3 interacts with NOM1, an eIF4G-like partner, in vitro and in vivo. Yeast Fal1p (eIF4A3 ortholog) interacts genetically with eIF4G-like Sgd1p. Knockdown of eIF4AIII and NOM1 in human cells demonstrates this conserved eIF4A/eIF4G-like complex acts in pre-rRNA processing. Human eIF4AIII complements the lethal phenotype and 18S rRNA biogenesis defect of fal1Δ yeast. Yeast complementation, genetic suppressor screen, in vitro pulldown, Co-IP in human cells, siRNA knockdown with rRNA processing readout Genes & development High 21576267
2011 eIF4A3 binds SECIS elements from non-essential selenoproteins at internal and apical loops, acting as a transcript-selective translational repressor of selenoprotein synthesis during selenium deficiency. Both globular domains of eIF4A3 are critical for SECIS binding; a uridine in the SECIS core is required for complex stability. RNA gel shifts, surface plasmon resonance, enzymatic footprinting, domain truncation analysis Nucleic acids research High 21685449
2012 CWC22 is a splicing factor and direct eIF4A3 binding partner that escorts eIF4A3 to spliceosomes and promotes EJC assembly. Recombinant CWC22 directly contacts eIF4A3 and prevents it from binding RNA. In vitro splicing assays show CWC22 introduces eIF4A3 to spliceosomes before remodeling; CWC22 knockdown abolishes EJC assembly in vivo. Recombinant protein direct binding assay, in vitro splicing assay, RNAi knockdown, Co-IP, mass spectrometry Nature structural & molecular biology High 22961380 25870412
2013 Crystal structure of human eIF4AIII-CWC22 MIF4G domain complex at 2.0 Å resolution reveals that CWC22 binds both RecA domains of eIF4AIII; the RNA-binding and ATP-binding motifs of the two RecA domains are held in diametrically opposite (inactive) positions, explaining how CWC22 inhibits eIF4AIII helicase activity. X-ray crystallography at 2.0 Å resolution 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), an acrofacial dysostosis. EIF4A3 transcript levels are reduced in affected individuals. Knockdown of eif4a3 in zebrafish causes underdevelopment of craniofacial cartilage and bone, demonstrating a role in mandible, laryngeal, and limb morphogenesis. Identity-by-descent mapping, sequencing, qRT-PCR in patient cells, zebrafish morpholino knockdown with skeletal phenotyping American journal of human genetics High 24360810
2014 eIF4AIII promotes efficient translation of mRNAs bound by the nuclear cap-binding complex (CBC) by unwinding secondary structures in 5' UTR. eIF4AIII is recruited to the 5'-end of CBC-bound mRNAs via direct interaction with CTIF (CBC-dependent translation initiation factor), independent of deposited EJCs. Polysome fractionation, tethering, and in vitro reconstitution confirm this translational enhancement. Polysome fractionation, tethering assay, in vitro reconstitution with recombinant proteins, Co-IP, RNA structure probing Proceedings of the National Academy of Sciences of the United States of America High 25313076
2015 CWC22 orchestrates both pre-mRNA splicing and eIF4A3 binding to achieve global EJC assembly. An eIF4A3-binding deficient CWC22 mutant impairs EJC assembly without affecting splicing, functionally uncoupling the two processes. A C-terminal domain of CWC22 enhances spliceosomal interaction. CWC22 domain mutagenesis, in vitro splicing assay, high-throughput RNA-seq, EJC assembly assay Nucleic acids research High 25870412
2017 Novel 1,4-diacylpiperazine derivatives are selective eIF4A3 inhibitors. SPR biosensing confirms direct binding to eIF4A3 at a non-ATP binding (allosteric) site. Cellular NMD inhibitory activity confirmed, providing first selective chemical probes for eIF4A3. High-throughput screening, SPR binding assay, cellular NMD reporter assay Journal of medicinal chemistry Medium 28358513
2017 ATP-competitive eIF4A3 inhibitors with submicromolar ATPase inhibitory activity and selectivity over other helicases were identified, confirming that the ATPase activity of eIF4A3 can be selectively targeted. ATPase inhibition assay, selectivity panel against other helicases Bioorganic & medicinal chemistry Medium 28283335
2017 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 MDM2 transcript isoforms that control p53. Nucleolar fractionation, R-loop detection, multilevel omics (transcriptomics, proteomics, ribosome profiling), siRNA knockdown Science advances Medium 34348895
2019 Threonine 163 (T163) 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, and instead promotes association with CWC22 to guide eIF4A3 to the active spliceosome. This ensures fidelity of EJC deposition and consequently affects NMD efficiency. Phospho-site identification, CDK1/2 in vitro kinase assay, Co-IP, NMD reporter assay, cell cycle synchronization Cell reports High 30784594
2019 EIF4A3 inhibition suppresses stress granule induction and maintenance, in part through EIF4A3-associated regulation of G3BP1 and TIA1 scaffold protein expression. EIF4A3 also controls cell cycle progression through its splicing activity. Small molecule EIF4A3 inhibitors, transcriptome-wide RNA-seq, stress granule imaging, cell cycle analysis Communications biology Medium 31069274
2019 Avian influenza A virus polymerase subunits PB2, PB1, and NP co-precipitate with eIF4A3. eIF4A3 depletion reduces viral RNA polymerase activity, viral RNA synthesis, and impairs M2/NS2 spliced mRNA nuclear export, leading to reduced virus replication. Co-immunoprecipitation with mass spectrometry, siRNA knockdown, viral replication assay, spliced/unspliced mRNA ratio quantification Frontiers in microbiology Medium 31379779
2016 eIF4A3 is required for efficient human cytomegalovirus (HCMV) replication. eIF4A3 depletion limits viral DNA accumulation and nuclear export of viral mRNAs but is dispensable for association of viral transcripts with ribosomes. siRNA knockdown of eIF4A3 in HCMV-infected cells, viral DNA quantification, nuclear/cytoplasmic mRNA fractionation, polysome association assay Virology Medium 26773380
2017 EIF4A3 deficiency in patient-derived iPSCs and conditional mouse models demonstrates that defective neural crest cell (NCC) development underlies Richieri-Costa-Pereira syndrome craniofacial abnormalities. RCPS NCCs have decreased migratory capacity; Eif4a3 haploinsufficiency causes mandibular defects in a NCC-autonomous manner; NCC-derived mesenchymal cells show premature bone differentiation. Patient iPSC-derived NCCs, conditional mouse knockout, neural crest cell migration assay, bone differentiation assay, NCC-specific Eif4a3 haploinsufficiency Human molecular genetics High 28334780
2021 EIF4A3 depletion leads to dephosphorylation and nuclear translocation of TFEB, the master autophagy transcription factor, inducing autophagosome and lysosome biogenesis and enhanced autophagic flux. Mechanistically, EIF4A3 controls TFEB via maintaining correct splicing of GSK3B (the direct TFEB kinase); its depletion causes an exon-skipping event reducing GSK3B expression and activity. siRNA knockdown, autophagy flux assay (autophagosome/lysosome markers), TFEB phosphorylation and nuclear translocation assay, splicing analysis of GSK3B, TCGA data analysis Cell death and differentiation High 34158631
2021 EIF4A3 resides in nucleoli and regulates rRNA processing. Its depletion impairs ribosome biogenesis checkpoint-mediated p53 induction and alters translation of MDM2 isoforms controlling p53, leading to cell cycle arrest. Nucleolar co-localization (live imaging/fractionation), rRNA processing assay, ribosome profiling, proteomics, siRNA knockdown Science advances Medium 34348895
2022 EIF4A3 is essential for maintenance of embryonic stem cell pluripotency. Mechanistically, eIF4A3 is required for efficient nuclear export of Ccnb1 mRNA (encoding Cyclin B1), a key pluripotency-promoting cell cycle regulator; its depletion causes loss of pluripotency via cell cycle dysregulation. RNAi screen, ESC pluripotency markers, mRNA nuclear export assay (nuclear/cytoplasmic fractionation), cell cycle analysis Nucleic acids research Medium 36416264
2022 EIF4A3 acts as an oncogene in hepatocellular carcinoma through modulation of FGFR4 splicing. EIF4A3 silencing alters FGFR4 splicing, blocks cellular response to FGF19 (FGFR4's natural ligand), and restoration of non-spliced FGFR4 full-length version blunts these effects. siRNA knockdown in HCC cell lines, xenograft model, RNA-seq splice analysis, FGFR4 inhibitor epistasis, FGFR4 rescue experiment Clinical and translational medicine Medium 36419260
2023 eIF4A3 directly interacts with eIF3g (a subunit of the eIF3 complex), and this interaction serves as a molecular linker between eIF4A3 and eIF3 to facilitate internal ribosomal entry on circRNAs. In vitro-synthesized circRNA translation assays demonstrate eIF4A3-driven internal translation dependent on the eIF4A3-eIF3g interaction. Transcriptome-wide analysis shows efficient polysomal association of endogenous circRNAs requires eIF4A3. Co-IP identifying eIF3g as eIF4A3 binding partner, in vitro circRNA translation reconstitution, polysome profiling, transcriptome-wide ribosome association analysis Nucleic acids research High 37811880
2023 EIF4A3 controls the EJC's role in promoting cortical progenitor mitosis. Eif4a3 haploinsufficiency in mice impairs neurogenesis by prolonging mitosis length, causing cell death and influencing progeny fate. These phenotypes are conserved in human cortical organoids from RCPS iPSCs. Rescue experiments show EIF4A3 controls neuron generation via the EJC. Conditional mouse haploinsufficiency, live imaging of neural progenitor mitosis, cortical organoid assay from patient iPSCs, Eif4a3;p53 compound mouse genetics, EJC rescue experiments Development (Cambridge, England) High 37139782
2024 EIF4A3 directly binds microtubules independently of RNA or the EJC, and this interaction promotes microtubule polymerization, regulates microtubule dynamics in neurons, and is required for axon growth. Biochemistry and competition experiments demonstrate EIF4A3-microtubule binding is mutually exclusive of EJC complex formation. In vitro reconstitution assays show EIF4A3 is sufficient to promote microtubule polymerization. In vitro microtubule reconstitution assay, direct biochemical binding assay (competition experiments), live imaging of microtubule dynamics in neurons, EIF4A3 disease mutant analysis in cortical organoids Cell reports High 39182224
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 in vertebrate embryogenesis. Morpholino knockdown in Xenopus laevis, phenotypic analysis Developmental dynamics Medium 20549732
2012 Eif4a3 knockdown in Xenopus causes incorrect splicing of ryanodine receptor (ryr) transcripts, leading to failure of calcium-dependent calcium release in muscle cells and embryonic paralysis, demonstrating a role for EJC in accurate pre-mRNA splicing during early embryogenesis. Morpholino knockdown, RT-PCR splicing analysis, calcium imaging in muscle cells, electrophysiology Developmental biology Medium 22944195
2011 EIF4A3 binds and stabilizes lncRNAs LINC00680 and TTN-AS1 by prolonging their half-life in glioblastoma cells, acting as an RNA-binding protein that modulates lncRNA stability. RNA immunoprecipitation (RIP), mRNA stability assay (actinomycin D), siRNA knockdown Molecular therapy. Nucleic acids Low 32000032
2021 EIF4A3 binds to beclin1 and FOXO1 mRNAs; a circRNA (hsa_circ_0030042) acts as an eIF4A3 sponge to block EIF4A3 recruitment to these mRNAs, thereby inhibiting ox-LDL-induced autophagy in endothelial cells. RNA immunoprecipitation, immunofluorescence, loss-of-function assays, autophagy flux assay Theranostics Low 33859754
2023 EIF4A3 interacts with FLOT1 (Flotillin-1) protein in lung adenocarcinoma cells and positively regulates FLOT1 protein expression, subsequently activating the PI3K-AKT-ERK1/2-P70S6K pathway. Mass spectrometry, Co-IP, siRNA knockdown, transcriptome sequencing Molecular cancer research : MCR Low 37011005
2021 CASC11 lncRNA recruits EIF4A3 to enhance the stability of E2F1 mRNA in hepatocellular carcinoma, demonstrating EIF4A3's role as an mRNA stabilizing factor for specific transcripts. RNA-binding protein immunoprecipitation (RIP), mRNA stability assay, ChIP assay, rescue experiments Clinical and translational medicine Low 33252856
2024 Under hypoxic conditions, the interaction between YAP1 and EIF4A3 is enhanced (demonstrated by co-immunoprecipitation), displacing EIF4A3 from binding to CRIM1 pre-mRNA and facilitating back-splicing of CRIM1 pre-mRNA to form circ_0007386. Co-immunoprecipitation under hypoxia, RNA immunoprecipitation, competitive binding assay Journal of experimental & clinical cancer research Low 39030638
2024 A circRNA (hsa_circ_0000467) binds eIF4A3 and suppresses its nuclear translocation, while also acting as a scaffold that bridges eIF4A3 and c-Myc mRNA in the cytoplasm, promoting c-Myc translation via enhanced polysomal association. RNA pull-down, RIP, immunofluorescence for eIF4A3 distribution, polysome profiling, dual-luciferase assay Molecular cancer Low 39085875

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 347 32264877
2004 An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 303 14973490
2018 EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. Molecular cancer 275 30470262
2005 The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nature structural & molecular biology 274 16170325
2004 eIF4A3 is a novel component of the exon junction complex. RNA (New York, N.Y.) 223 14730019
2004 eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nature structural & molecular biology 215 15034551
2022 EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling. Cancer research 182 34965937
2021 EIF4A3-induced circular RNA ASAP1 promotes tumorigenesis and temozolomide resistance of glioblastoma via NRAS/MEK1/ERK1-2 signaling. Neuro-oncology 170 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 98 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 94 24360810
2021 hsa_circ_0068631 promotes breast cancer progression through c-Myc by binding to EIF4A3. Molecular therapy. Nucleic acids 84 34513299
2018 Sanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 80 29571014
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 71 35513835
2020 Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3-mediated E2F1 activation. Clinical and translational medicine 67 33252856
2019 EIF4A3-Induced circ-BNIP3 Aggravated Hypoxia-Induced Injury of H9c2 Cells by Targeting miR-27a-3p/BNIP3. Molecular therapy. Nucleic acids 63 31923741
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 62 25313076
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
2023 Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205. Cell death discovery 59 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 58 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
2020 Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes. The EPMA journal 51 32549918
2019 LINC00680 and TTN-AS1 Stabilized by EIF4A3 Promoted Malignant Biological Behaviors of Glioblastoma Cells. Molecular therapy. Nucleic acids 47 32000032
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 46 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
2017 EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome. Human molecular genetics 40 28334780
2013 Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Organic letters 40 23461621
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 39 37280654
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
2020 LINC00667 promotes the proliferation, migration, and pathological angiogenesis in non-small cell lung cancer through stabilizing VEGFA by EIF4A3. Cell biology international 39 32281700
2019 eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle. Cell reports 39 30784594
2024 EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cisplatin resistance. Journal of experimental & clinical cancer research : CR 38 38163881
2023 EIF4A3-induced circZFAND6 promotes breast cancer proliferation and metastasis through the miR-647/FASN axis. Life sciences 37 37127184
2022 EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway. Cell death discovery 37 35236829
2021 CircRNA_100290 promotes GC cell proliferation and invasion via the miR-29b-3p/ITGA11 axis and is regulated by EIF4A3. Cancer cell international 37 34182990
2022 CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3. Experimental cell research 36 35752345
2021 EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression. Cell death & disease 35 34716310
2022 LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability. Cellular & molecular biology letters 34 36221055
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
2019 Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation. Communications biology 33 31069274
2023 EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression. Cell death & disease 32 37626035
2024 Circular RNA hsa_circ_0000467 promotes colorectal cancer progression by promoting eIF4A3-mediated c-Myc translation. Molecular cancer 31 39085875
2023 An interaction between eIF4A3 and eIF3g drives the internal initiation of translation. Nucleic acids research 31 37811880
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
2023 EIF4A3-Induced Exosomal circLRRC8A Alleviates Granulosa Cells Senescence Via the miR-125a-3p/NFE2L1 axis. Stem cell reviews and reports 28 37243831
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
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-regulated circRABL2B regulates cell stemness and drug sensitivity of lung cancer via YBX1-dependent downregulation of MUC5AC expression. International journal of biological sciences 24 37324942
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
2021 eIF4A3 regulates the TFEB-mediated transcriptional response via GSK3B to control autophagy. Cell death and differentiation 22 34158631
2021 EIF4A3: a gatekeeper of autophagy. Autophagy 22 34643458
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
2022 EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma. Cellular and molecular life sciences : CMLS 21 35680727
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
2016 The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication. Virology 20 26773380
2024 EIF4A3-Induced Circular RNA CircDdb1 Promotes Muscle Atrophy through Encoding a Novel Protein CircDdb1-867aa. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 39412095
2022 EIF4A3-induced circCCNB1 (hsa_circ_0001495) promotes glioma progression by elevating CCND1 through interacting miR-516b-5p and HuR. Metabolic brain disease 19 35038081
2011 Identification of a signature motif for the eIF4a3-SECIS interaction. Nucleic acids research 19 21685449
2020 lncRNA HOXC-AS1 promotes gastric cancer via binding eIF4AIII by activating Wnt/β-catenin signaling. The journal of gene medicine 18 32307743
2025 EIF4A3-Mediated Biogenesis of CircFADS1 Promotes the Progression of Hepatocellular Carcinoma via Wnt/β-Catenin Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39965082
2023 EIF4A3 induced circABCA5 promotes the gastric cancer progression by SPI1 mediated IL6/JAK2/STAT3 signaling. American journal of cancer research 17 36895988
2023 Exosomal circCOL1A1 promotes angiogenesis via recruiting EIF4A3 protein and activating Smad2/3 pathway in colorectal cancer. Molecular medicine (Cambridge, Mass.) 17 37940881
2024 EIF4A3 modulated circ_000999 promotes epithelial-mesenchymal transition in cadmium-induced malignant transformation through the miR-205-5p/ZEB1 axis. Environment international 16 38621321
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
2023 The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis. Development (Cambridge, England) 15 37139782
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
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
2021 EIF4A3-mediated hsa_circ_0088088 promotes the carcinogenesis of breast cancer by sponging miR-135-5p. Journal of biochemical and molecular toxicology 14 34463003
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
2022 Plasmacytoma variant translocation 1 stabilized by EIF4A3 promoted malignant biological behaviors of lung adenocarcinoma by generating circular RNA LMNB2. Bioengineered 13 35435126
2021 The EIF4A3/CASC2/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas. Frontiers in oncology 13 34408982
2020 Correction to: EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. Molecular cancer 13 33126881
2024 EIF4A3-Induced CircDHTKD1 regulates glycolysis in non-small cell lung cancer via stabilizing PFKL. Journal of cellular and molecular medicine 12 39022816
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 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
2025 SP-1-activated LINC01016 overexpression promotes gastric cancer invasion and metastasis through inhibiting EIF4A3-mediated MMP9 mRNA decay. Cell death & disease 11 39881131
2024 EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway. Cell biology and toxicology 11 39382613
2021 hsa_circ_0101119 facilitates the progression of cervical cancer via an interaction with EIF4A3 to inhibit TCEAL6 expression. Molecular medicine reports 11 34278492
2021 The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway. Frontiers in oncology 11 34868959
2017 Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors. ACS medicinal chemistry letters 11 29057054
2024 EIF4A3-Induced Circ_0059914 Promoted Angiogenesis and EMT of Glioma via the miR-1249/VEGFA Pathway. Molecular neurobiology 9 38951469

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