Affinage

EIF3A

Eukaryotic translation initiation factor 6 · UniProt P56537

Length
245 aa
Mass
26.6 kDa
Annotated
2026-06-09
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF3A (eIF3a/TIF32/p170) is the largest subunit of the eukaryotic translation initiation factor 3 (eIF3) complex and functions as a central scaffold for translation initiation and a selective regulator of mRNA-specific translation (PMID:10358023, PMID:22135459). As an essential, conserved subunit, EIF3A is required for the integrity and ribosome-binding activity of eIF3; its depletion in yeast causes ribosome runoff from polysomes, and it nucleates assembly of the octameric eIF3 module in human cells together with eIF3b (PMID:10358023, PMID:27924037). EIF3A makes multiple direct contacts that organize the 43S preinitiation complex: its N-terminal domain binds ribosomal protein RPS0A near the mRNA exit channel, its C-terminal domain contacts 18S rRNA helices 16–18 as well as RPS2/RPS3 near the mRNA entry channel, and both termini engage eIF1, eIF5, and the eIF2/GTP/Met-tRNAi ternary complex to position initiation factors across the 40S subunit (PMID:12651896, PMID:20584985, PMID:22792338, PMID:25171412). RNA-binding surfaces within its PCI domain and CTD, including residues R363/K364 and a KERR motif, are required for mRNA recruitment to and scanning/start-codon recognition by the 43S complex (PMID:20584985, PMID:24423867, PMID:23766293). Beyond canonical initiation, EIF3A within eIF3 selectively controls translation of defined mRNA programs through 5'-UTR stem-loop and IRES-like elements, acting as either an activator (c-JUN) or repressor (BTG1, FTL), the latter via a mechanism whose disruption by FTL 5'-UTR SNPs causes hyperferritinemia (PMID:25849773, PMID:31953146, PMID:31414986). EIF3A also remains associated with ribosomes elongating short upstream ORFs to enable post-termination reinitiation in a manner dependent on its N-terminal domain and cis-acting 5'-UTR reinitiation-promoting elements, a mechanism conserved from yeast GCN4 to human ATF4 (PMID:18765792, PMID:21750682, PMID:28119417, PMID:28745933). Through these activities EIF3A tunes synthesis of specific targets—including nucleotide excision repair proteins, RPA2, HIF1α, c-Myc, and TCR subunits—in response to iron depletion, DNA damage, mTOR signaling, and immune co-stimulation, linking it to cell-cycle progression, DNA repair, chemosensitivity, and oncogenic transformation (PMID:21625209, PMID:23393223, PMID:31218114, PMID:34970966, PMID:17170115).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 Medium

    Establishing EIF3A as a bona fide integral subunit of human eIF3 was the necessary first step, defining it as part of the ribosome-associated initiation machinery rather than a peripheral factor.

    Evidence Co-immunoprecipitation with anti-p170 antibodies and ribosome fractionation in human cells

    PMID:8995409

    Open questions at the time
    • Did not map which subunits EIF3A directly contacts
    • No functional role for EIF3A established
  2. 1999 High

    Genetic essentiality of the yeast ortholog TIF32 showed EIF3A is required for the initiation phase of translation, not merely a structural passenger.

    Evidence Gene deletion/depletion with polysome profiling, co-IP, far Western, and two-hybrid in yeast

    PMID:10358023

    Open questions at the time
    • Specific ribosomal and factor contacts not yet mapped
    • Did not address selective mRNA regulation
  3. 2003 High

    Domain-resolved mapping defined how EIF3A physically organizes the preinitiation complex, contacting both the 40S ribosome (RPS0A, 18S rRNA) and the eIF1/eIF5/ternary complex, explaining its scaffolding role.

    Evidence In vitro binding with purified domains and in vivo affinity pulldown in yeast (building on CTD–eIF2 contact mapping)

    PMID:12411506 PMID:12651896

    Open questions at the time
    • Structural detail of these contacts not yet resolved
    • How contacts are coordinated during scanning unknown
  4. 2010 High

    Identification of the CTD KERR/box6 elements and RPS2/RPS3 binding placed EIF3A at the mRNA entry channel and assigned it a direct role in mRNA recruitment and start-codon recognition fidelity.

    Evidence Site-directed mutagenesis with in vivo mRNA recruitment and scanning-fidelity assays in yeast

    PMID:20584985

    Open questions at the time
    • Atomic structure of CTD–rRNA/RPS contacts not resolved here
    • Quantitative contribution to scanning kinetics unclear
  5. 2014 High

    Crystal and integrative structures defined the PCI/MPN core architecture and showed eIF3 (with EIF3A) clamps the 40S subunit, positioning factors at opposite ends of the mRNA channel and identifying RNA-binding residues required for mRNA recruitment.

    Evidence X-ray crystallography of the EIF3A PCI domain plus EM, cross-linking MS, and integrative modeling, with mutagenesis

    PMID:24423867 PMID:25171412

    Open questions at the time
    • Higher-resolution placement of EIF3A flexible domains incomplete
    • Dynamics during scanning not captured
  6. 2015 High

    Cryo-EM of the 43S complex and reconstitution of binding cooperativity established how EIF3-containing eIF3 stabilizes the assembled preinitiation complex and recruits eIF1/eIF1A/ternary complex.

    Evidence Cryo-EM of DHX29-bound 43S and fluorescence-anisotropy reconstitution with defined components

    PMID:25246524 PMID:26344199

    Open questions at the time
    • Subunit-specific allostery of EIF3A within these transitions unresolved
  7. 2016 High

    Systematic subunit knockdown showed EIF3A nucleates the octameric eIF3 module in human cells, establishing its hierarchical role in complex assembly.

    Evidence RNAi knockdown of each subunit with co-IP and Western assessment in human cells

    PMID:27924037

    Open questions at the time
    • Whether assembly subcomplexes have distinct regulatory functions not defined here
  8. 2008 High

    Discovery that the EIF3A NTD binds GCN4 mRNA sequences 5' of uORF1 and is required for resumption of scanning revealed a role beyond canonical initiation: enabling reinitiation after uORF translation.

    Evidence Yeast genetics, in vivo ribosome association, and epistasis with 5' enhancer sequences (extended by RPE characterization in 2011)

    PMID:18765792 PMID:21750682

    Open questions at the time
    • Mechanism by which eIF3 stays associated during elongation not yet shown
    • Conservation in mammals not yet tested at this stage
  9. 2015 High

    Genome-wide PAR-CLIP demonstrated EIF3-containing eIF3 binds a specific program of 5'-UTR stem-loops to activate or repress defined mRNAs, defining selective translational control as a core EIF3A function.

    Evidence PAR-CLIP with functional translation reporter assays (later refined by NMR of the c-JUN stem-loop)

    PMID:25849773 PMID:31953146

    Open questions at the time
    • How activation vs. repression mode is selected at each mRNA not fully resolved
    • Subunit-specific RNA contact within the complex incompletely defined
  10. 2017 High

    Direct in vivo detection of eIF3 on 80S ribosomes elongating short uORFs provided physical evidence that EIF3A travels with elongating ribosomes, mechanistically grounding reinitiation, with conservation extending to human ATF4.

    Evidence Novel in vivo RNA-protein Ni2+-pulldown with genetic RPE/TIF32 controls; mammalian reporter assays

    PMID:28119417 PMID:28745933

    Open questions at the time
    • Threshold of uORF length tolerated mechanistically undefined
    • Factors handing off eIF3 at termination not identified
  11. 2019 High

    Establishing eIF3-mediated FTL repression and its disruption by hyperferritinemia SNPs provided the first direct causal link between EIF3A/eIF3 translational control and human disease.

    Evidence PAR-CLIP, ribosome profiling, reporter assays, and SNP functional analysis

    PMID:31414986

    Open questions at the time
    • Whether EIF3A specifically contacts the FTL element not isolated from the complex
    • Therapeutic relevance unexplored in this corpus
  12. 2020 High

    Ribosome profiling and 80S co-IP showed eIF3 regulates early elongation speed and recruits quality-control factors, with knockout causing mitochondrial defects, extending EIF3A function into co-translational control and tissue physiology.

    Evidence Ribosome profiling, 80S Co-IP, and eIF3e+/- mouse model with mitochondrial physiology assays

    PMID:32589965

    Open questions at the time
    • EIF3A-specific contribution within the eIF3e-deficient phenotype not isolated
    • Identity of recruited QC factors only partly defined
  13. 2022 Medium

    Linking EIF3A to m6A/m5C reader machinery (YTHDF3 recruitment, NOP2-dependent c-Myc destabilization) connected EIF3A to RNA-modification-dependent translational and stability control in cancer.

    Evidence Co-IP, RIP-seq/RIP, translation and mRNA stability assays with knockdown (2022 and 2023 studies)

    PMID:35708211 PMID:37398932

    Open questions at the time
    • Direct vs. indirect nature of EIF3A–m6A/m5C effects not fully resolved
    • Single-lab observations without reciprocal structural validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EIF3A's selective recognition of distinct 5'-UTR/3'-UTR elements is regulated by signaling inputs (iron, DNA damage, mTOR, CD28) to switch between activation, repression, and reinitiation of specific mRNAs remains incompletely defined.
  • No unified model linking signal-dependent EIF3A modification to target selection
  • Subunit-resolved RNA contacts within intact eIF3 for most regulated mRNAs unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0045182 translation regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005840 ribosome 5 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3
Partners
EIF1EIF2EIF3BEIF4BMTORRPS0ARPS3YTHDF3
Complex memberships
43S preinitiation complexeIF3 complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 eIF4B directly interacts with the p170 subunit of eIF3 (EIF3A) via a DRYG domain, suggesting eIF4B acts as an intermediary between mRNA and eIF3 during 40S ribosome binding. Filter overlay (far Western) assay and yeast two-hybrid system Molecular and cellular biology Medium 8816444
1997 EIF3A (p170) is an integral subunit of human eIF3 that co-immunoprecipitates with p116, p110, and p36 subunits; p116, p110, and p36 localize on 40S ribosomes in translation-active cells. Co-immunoprecipitation with affinity-purified anti-p170 antibodies; ribosome localization by cell fractionation The Journal of biological chemistry Medium 8995409
1998 EIF3A (p44 subunit interaction): eIF3-p44 interacts strongly and specifically with the eIF3-p170 subunit (EIF3A) by far Western analysis, and p44 also binds 18S rRNA and beta-globin mRNA via an RNA recognition motif. Far Western (protein-protein overlay) assay; Northwestern blotting The Journal of biological chemistry Medium 9822659
1999 TIF32 (yeast EIF3A ortholog, p110 subunit) is an essential eIF3 subunit; its deletion is lethal and its depletion causes runoff of ribosomes from polysomes, indicating an initiation-phase defect. TIF32 directly interacts with p90 (eIF3b ortholog) by far Western and two-hybrid analyses. Gene deletion/depletion (polysome profiling), co-immunoprecipitation, far Western, two-hybrid The Journal of biological chemistry High 10358023
1999 The intracellular domain of rat trkA kinase interacts with the p162 subunit of eIF3 (EIF3A) in an activity-dependent manner, identified by yeast two-hybrid screening. Yeast two-hybrid screen Journal of molecular neuroscience : MN Low 10691301
2001 The RNA recognition motif (RRM) of eIF3 subunit PRT1 (eIF3b) simultaneously interacts with HCR1 and with an internal domain of TIF32 (EIF3A); removal of the PRT1 RRM caused dissociation of TIF32 and destroyed 40S ribosome binding, establishing the PRT1 RRM as crucial for eIF3 integrity and ribosome-binding activity. Yeast genetic suppressor analysis; co-immunoprecipitation; in vitro binding assays; 40S ribosome binding assays The EMBO journal High 11179233
2001 The foot-and-mouth disease virus (FMDV) IRES interacts with a 116/110 kDa doublet that is a component of eIF3, with domain 5 of the IRES holding the preferential binding site for eIF3. UV crosslinking; immunoblotting; competition binding assays RNA (New York, N.Y.) Medium 11565745
2001 Approximately 20% of EIF3A (p170) is associated with membranes (ER and plasma membranes) via actin filaments, while the remainder is cytoplasmic; membrane-bound p170 is not phosphorylated whereas cytoplasmic p170 is phosphorylated at serine/threonine residues in a serum-stimulated manner. Subcellular fractionation; immunofluorescence; phosphorylation analysis (serum stimulation) European journal of cell biology Medium 11484932
2002 The C-terminal domain (CTD) of TIF32 (EIF3A) directly binds eIF2, providing an independent eIF2–eIF3 contact that is required for eIF2–eIF3 association in vivo; this contact is additive with the NIP1-eIF5-eIF2 connection for translation initiation. In vivo affinity pulldown with tagged subunit deletion mutants; genetic (overexpression) epistasis The EMBO journal High 12411506
2003 The N-terminal domain (NTD) of TIF32/eIF3a interacts with small ribosomal protein RPS0A located near the mRNA exit channel; the CTD of TIF32 interacts with helices 16–18 of 18S rRNA; both the N-terminal domain of NIP1 and the CTD of TIF32 interact with eIF1, eIF5, and the eIF2/GTP/Met-tRNAi ternary complex. In vitro binding assays with purified domains; in vivo affinity pulldown Genes & development High 12651896
2003 EIF3A (p170) mediates the effect of mimosine on mRNA translation; mimosine reduces p170 translation (via iron chelation), which causes decreased synthesis of tyrosinated alpha-tubulin and elevated translation of p27, preceding cell cycle arrest. Western blot; [35S]-methionine incorporation; iron chelation experiments; cell cycle analysis Molecular biology of the cell Medium 12972576
2004 Altering EIF3A (p170) expression level changes the synthesis rate of ribonucleotide reductase M2 (RRM2) and DNA synthesis; decreasing p170 in H1299 and MCF7 cells reversed their malignant growth phenotype, while overall protein synthesis was only ~25% reduced, suggesting p170 regulates translation of a subset of mRNAs. RNAi knockdown; [35S]-methionine incorporation; [3H]-thymidine incorporation; cell growth assays Oncogene Medium 15094776
2006 mTOR directly interacts with eIF3 and controls the association of eIF3 and eIF4G in an insulin/mTOR-dependent, rapamycin-sensitive manner; this eIF4G–eIF3 association does not require eIF4E binding to eIF4G nor eIF3 binding to the 40S subunit. Co-immunoprecipitation; rapamycin/insulin treatment; pharmacological inhibitor assays The EMBO journal Medium 16541103
2006 Ectopic overexpression of EIF3A in NIH3T3 cells stimulates translation initiation and global protein synthesis, enhances translation of poorly translated mRNAs encoding cyclin D1, c-Myc, FGF-2, and ornithine decarboxylase, and induces oncogenic transformation. Stable transfection; [35S]-methionine incorporation; polysome profiling; focus formation; soft agar assay The Journal of biological chemistry Medium 17170115
2007 EIF3A (p170) expression decreases during intestinal cell differentiation; enforced EIF3A expression inhibits Caco-2 differentiation whereas knockdown promotes differentiation, placing EIF3A as a regulator of intestinal epithelial cell differentiation. siRNA knockdown; ectopic expression; differentiation assays in colon cell lines; mouse developmental expression analysis Differentiation; research in biological diversity Medium 17381544
2008 The N-terminal domain (NTD) of eIF3a/TIF32 interacts with sequences 5' of uORF1 in GCN4 mRNA; partial deletion of the RPS0A-binding domain of eIF3a impairs eIF3 binding to preinitiation complexes in vivo and severely blocks GCN4 translational induction by reinitiation, revealing that eIF3a is required for post-termination resumption of scanning at uORF1. Yeast genetics; in vivo ribosome association assays; genetic epistasis with 5' enhancer sequences Genes & development High 18765792
2009 EIF3A expression oscillates during the cell cycle, peaking in S phase; reducing EIF3A expression prolongs the cell cycle without changing cell cycle distribution, and EIF3A affects cellular response to external cell cycle modulators by altering synthesis of their target proteins. Flow cytometry; Western blot; siRNA knockdown; cell cycle synchronization Experimental cell research Medium 19327350
2010 The C-terminal domain (CTD) of yeast eIF3a/Tif32 contains a conserved KERR motif and box6 element that are required for mRNA recruitment by 43S preinitiation complexes and for scanning fidelity and start codon recognition; the eIF3a CTD also binds ribosomal proteins Rps2 and Rps3, placing it near the mRNA entry channel. Site-directed mutagenesis; in vivo mRNA recruitment assays; genetic epistasis; in vitro binding assays Molecular and cellular biology High 20584985
2011 EIF3A knockdown or overexpression, respectively, increases or decreases DNA repair activity and the synthesis of nucleotide excision repair (NER) proteins (XPA, XPC, RAD23B, RPA32), thereby affecting cellular sensitivity to cisplatin. siRNA knockdown; ectopic overexpression; host-cell reactivation assay (DNA repair); Western blot; MTT assay Oncogene Medium 21625209
2011 EIF3A knockdown increased NER protein synthesis and repair capacity in lung cancer cells, increasing resistance to cisplatin and anthracyclines; conversely, EIF3A overexpression decreased NER protein levels, thereby sensitizing cells to DNA-damaging drugs. siRNA knockdown; ectopic overexpression; host-cell reactivation assay; Western blot; MTT assay Clinical cancer research Medium 21610145
2011 Functional reconstitution of human 13-subunit eIF3 in E. coli revealed that the eight structurally conserved subunits form the core that binds the 40S ribosomal subunit, cap-dependent initiation factors, and HCV IRES RNA; the remaining subunits enable assembly of intact initiation complexes with HCV IRES. Recombinant reconstitution in E. coli; 40S binding assays; HCV IRES binding assays; negative-stain EM Proceedings of the National Academy of Sciences of the United States of America High 22135459
2011 Reinitiation after uORF1 translation in GCN4 mRNA depends on structurally defined reinitiation-promoting elements (RPEs) in the 5' enhancer that operate in an eIF3a/TIF32-dependent manner; two separate regions in the eIF3a/TIF32 NTD stimulate reinitiation in concert with the 5' enhancer. Yeast genetics; epistasis analysis; biochemical mRNA-protein interaction assays; computational structural modeling PLoS genetics High 21750682
2012 The N-terminal domain (NTD) of eIF3a/TIF32 (residues 200–400) specifically interacts with the C-terminal tail (CTT) of ribosomal protein RPS0A near the mRNA exit channel; depletion of RPS0A reduces eIF3 and associated eIFs on 40S subunits in preinitiation complexes. In vivo conditional depletion; co-immunoprecipitation; polysome profiling; domain-specific binding assays PloS one High 22792338
2013 Mutations in the RNA-binding motif of eIF3a weaken eIF3 binding to the HCV IRES and the 40S ribosomal subunit, suppressing eIF2-dependent recognition of the start codon, revealing a direct connection between the eIF3a RNA-binding motif and start codon recognition. Site-directed mutagenesis; EM; biochemical binding assays Nucleic acids research High 23766293
2013 EIF3A suppresses RPA2 synthesis and inhibits cellular IRES activity by directly binding to the IRES element of RPA2 mRNA located at -50 to -150 bases upstream of the translation start site; RPA2 expression is regulated at the translational level via IRES-mediated initiation in response to DNA damage. RNA immunoprecipitation; IRES reporter assays; siRNA knockdown; Western blot Carcinogenesis Medium 23393223
2013 EIF3A is recruited to stress granules during iron depletion, hypoxia, and tunicamycin treatment; it positively regulates NDRG1 expression and negatively regulates p27(kip1) expression during iron depletion, and positively regulates proliferation while negatively regulating cell motility and invasion. Inducible overexpression/ablation; immunofluorescence (stress granule co-localization); Western blot PloS one Medium 23437357
2014 Crystal structure of the eIF3a/TIF32 PCI domain at 2.65-Å resolution shows it is required for integrity of the eIF3 core; the PCI domain's positively charged surface (including residues R363 and K364) is capable of RNA binding, and mutation of these residues severely impairs mRNA recruitment to 43–48S PICs in vivo. X-ray crystallography; site-directed mutagenesis; in vivo mRNA recruitment assay Nucleic acids research High 24423867
2014 X-ray structures of yeast eIF3 core components, combined with EM, cross-linking MS, and integrative modeling, show that eIF3 engages the 40S subunit in a clamp-like manner, encircling it to position initiation factors on opposite ends of the mRNA channel; eIF3a is part of this extended modular arrangement. X-ray crystallography; cryo-EM; chemical cross-linking coupled to MS; integrative structure modeling Cell High 25171412
2015 Cryo-EM structure of eIF3 in the context of the DHX29-bound 43S complex at ~6 Å resolution reveals the PCI/MPN core organization of eIF3, including the positions and interactions of individual subunits (including eIF3a) with components of the 43S complex. Cryo-electron microscopy; near-complete polyalanine-level model building Nature High 26344199
2015 eIF3 (including eIF3a) binds to a specific program of mRNAs involved in cell growth control via their 5' UTR stem-loop structures, exerting either translational activation (c-JUN mRNA) or repression (BTG1 mRNA) through different modes of RNA stem-loop binding. PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation); functional translation reporter assays Nature High 25849773
2015 eIF3 dramatically increases the affinity of eIF1 and eIF3j for the 40S subunit; negative cooperativity exists between eIF3j binding and binding of eIF1, eIF1A, and the ternary complex; these interactions collectively stabilize the 43S preinitiation complex. Fluorescence anisotropy; reconstituted human 43S PIC assembly with defined components The Journal of biological chemistry High 25246524
2016 eIF3b and EIF3A (eIF3a) serve as the nucleation core for human eIF3 assembly in vivo; in the absence of eIF3b neither the yeast-like core nor the octamer forms, while EIF3A (eIF3a) nucleates the octamer module; disrupting the octamer produces subcomplexes with potential translational regulatory roles. RNAi knockdown of each subunit in human cells; co-immunoprecipitation; Western blot assessment of subunit levels Nucleic acids research High 27924037
2017 eIF3 (requiring the eIF3a/TIF32 subunit) remains bound to ribosomes elongating short uORFs and is detected on 80S ribosomes at reinitiation-permissive uORFs of GCN4 mRNA in vivo; this association requires intact 5' reinitiation-promoting elements (RPEs) and declines with extended uORF length. Novel in vivo RNA-protein Ni2+-pulldown assay; genetic analysis of RPE and eIF3a/TIF32 subunit Nucleic acids research High 28119417
2017 The molecular basis of reinitiation dependent on eIF3 and sequences flanking uORF1 is conserved between yeast and humans; eIF3 and sequences flanking the human ATF4 uORF1 (functional homolog of GCN4 uORF1) are required for efficient reinitiation in mammalian cells. Reporter assays in mammalian cells; siRNA knockdown; sequence mutagenesis RNA biology Medium 28745933
2019 Human eIF3 acts as a distinct repressor of ferritin light chain (FTL) mRNA translation; eIF3-mediated FTL repression is disrupted by a subset of SNPs in the FTL 5'-UTR that cause hyperferritinemia, establishing a direct causal link between eIF3-mediated translational control and human disease. PAR-CLIP; translation reporter assays; ribosome profiling; SNP functional analysis eLife High 31414986
2019 EIF3A regulates HIF1α protein synthesis through IRES-dependent translation; EIF3A depletion significantly reduces HIF1α protein level and cellular glycolysis capacity in hepatocellular carcinoma cells. siRNA knockdown; IRES reporter assays; Western blot; glycolysis measurement (ECAR) American journal of cancer research Medium 31218114
2020 eIF3 deficiency (eIF3e+/- mice) reduces early ribosomal elongation speed between codons 25 and 75 on ~2,700 mRNAs encoding mitochondrial and membrane-associated proteins; eIF3 interacts with 80S ribosomes translating the first ~60 codons and recruits protein quality-control factors, with loss causing defective mitochondria in skeletal muscle and progressive decline in muscle strength. Ribosome profiling; Co-IP of eIF3 with 80S ribosomes; mouse knockout model; mitochondrial physiology assays Molecular cell High 32589965
2020 NMR structure of a stem-loop in the c-JUN 5'-UTR shows structural similarity to eIF3-recognizing motifs in HCV-like IRESs; this stem-loop is essential for specialized eIF3-mediated translation initiation of c-JUN. NMR structure determination; mutational analysis of stem-loop; translation reporter assays Journal of molecular biology High 31953146
2021 Human eIF3 interacts with TCRA and TCRB mRNA 3'-UTRs in a CD28 co-receptor signaling-dependent manner, regulating a burst in TCR translation required for robust T cell activation. PAR-CLIP; translation reporter assays with TCRA/TCRB 3'-UTRs; CD28 signaling perturbation; ribosome profiling eLife High 34970966
2022 YTHDF3 recruits EIF3A to facilitate translation of m6A-methylated target mRNAs in oxaliplatin-resistant colorectal cancer cells; eIF2AK2 bridges YTHDF3 and EIF3A, enhancing stability of the YTHDF3/EIF3A complex. Co-immunoprecipitation; RIP-seq; translation assays; siRNA knockdown ACS chemical biology Medium 35708211
2023 NOP2-mediated m5C modification of c-Myc mRNA induces its degradation in an EIF3A-dependent manner; EIF3A is required for the m5C-dependent destabilization of c-Myc mRNA in hepatocellular carcinoma cells. m5C methylation assays; siRNA knockdown of EIF3A; mRNA stability assays; RIP Research (Washington, D.C.) Medium 37398932
2000 Yeast Rpg1p (TIF32/EIF3A ortholog) co-localizes with microtubules in budded cells and co-immunoprecipitates with alpha-tubulin from yeast cell-free extract; it co-sediments with hog brain microtubules in vitro, identifying EIF3A as a microtubule-interacting protein. Confocal microscopy; co-immunoprecipitation with anti-tubulin; microtubule co-sedimentation assay Cell motility and the cytoskeleton Medium 10706778

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3. Cell 738 9741626
2015 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature 343 25849773
2006 eIF3: a versatile scaffold for translation initiation complexes. Trends in biochemical sciences 318 16920360
2008 The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. The EMBO journal 257 18354498
2015 Structure of mammalian eIF3 in the context of the 43S preinitiation complex. Nature 216 26344199
2014 Molecular architecture of the 40S⋅eIF1⋅eIF3 translation initiation complex. Cell 178 25171412
2006 Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells. The Journal of biological chemistry 170 17170115
2013 Hepatitis-C-virus-like internal ribosome entry sites displace eIF3 to gain access to the 40S subunit. Nature 163 24185006
1996 A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3. Molecular and cellular biology 158 8816444
2003 The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment. The EMBO journal 141 12773399
2006 Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer. Critical reviews in oncology/hematology 129 16829125
2003 The yeast eIF3 subunits TIF32/a, NIP1/c, and eIF5 make critical connections with the 40S ribosome in vivo. Genes & development 128 12651896
1997 Conservation and diversity of eukaryotic translation initiation factor eIF3. The Journal of biological chemistry 127 8995409
2017 Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle. Nucleic acids research 121 28981723
2002 Direct eIF2-eIF3 contact in the multifactor complex is important for translation initiation in vivo. The EMBO journal 117 12411506
2008 eIF3a cooperates with sequences 5' of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA. Genes & development 111 18765792
2006 mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. The EMBO journal 107 16541103
2001 IRES interaction with translation initiation factors: functional characterization of novel RNA contacts with eIF3, eIF4B, and eIF4GII. RNA (New York, N.Y.) 103 11565745
2003 The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro. The Journal of biological chemistry 101 14688252
2011 Functional reconstitution of human eukaryotic translation initiation factor 3 (eIF3). Proceedings of the National Academy of Sciences of the United States of America 97 22135459
2009 PCI complexes: Beyond the proteasome, CSN, and eIF3 Troika. Molecular cell 97 19683491
2001 Related eIF3 subunits TIF32 and HCR1 interact with an RNA recognition motif in PRT1 required for eIF3 integrity and ribosome binding. The EMBO journal 96 11179233
2023 NOP2-mediated m5C Modification of c-Myc in an EIF3A-Dependent Manner to Reprogram Glucose Metabolism and Promote Hepatocellular Carcinoma Progression. Research (Washington, D.C.) 95 37398932
2002 A conserved RNA structure within the HCV IRES eIF3-binding site. Nature structural biology 95 11927954
2004 Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth. Oncogene 94 15094776
2014 The role of eIF3 and its individual subunits in cancer. Biochimica et biophysica acta 93 25450521
2003 EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression. Molecular biology of the cell 93 12972576
2013 Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells. PLoS genetics 92 24278036
2017 eIF3: a factor for human health and disease. RNA biology 87 29099306
2015 Structure of a yeast 40S-eIF1-eIF1A-eIF3-eIF3j initiation complex. Nature structural & molecular biology 84 25664723
2020 eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health. Molecular cell 83 32589965
2017 In vivo evidence that eIF3 stays bound to ribosomes elongating and terminating on short upstream ORFs to promote reinitiation. Nucleic acids research 81 28119417
2018 DDX3 Activates CBC-eIF3-Mediated Translation of uORF-Containing Oncogenic mRNAs to Promote Metastasis in HNSCC. Cancer research 79 29921696
2010 The C-terminal region of eukaryotic translation initiation factor 3a (eIF3a) promotes mRNA recruitment, scanning, and, together with eIF3j and the eIF3b RNA recognition motif, selection of AUG start codons. Molecular and cellular biology 79 20584985
2016 Human eIF3b and eIF3a serve as the nucleation core for the assembly of eIF3 into two interconnected modules: the yeast-like core and the octamer. Nucleic acids research 74 27924037
2013 Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation. Nucleic acids research 74 23766293
2011 Effect of eIF3a on response of lung cancer patients to platinum-based chemotherapy by regulating DNA repair. Clinical cancer research : an official journal of the American Association for Cancer Research 74 21610145
2017 MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway. Scientific reports 72 28074905
2011 Translation reinitiation relies on the interaction between eIF3a/TIF32 and progressively folded cis-acting mRNA elements preceding short uORFs. PLoS genetics 71 21750682
2001 Reduced expression of INT-6/eIF3-p48 in human tumors. International journal of oncology 71 11115556
2009 Role of eIF3a in regulating cell cycle progression. Experimental cell research 70 19327350
2011 Role of eIF3a in regulating cisplatin sensitivity and in translational control of nucleotide excision repair of nasopharyngeal carcinoma. Oncogene 68 21625209
2013 N-myc downstream regulated 1 (NDRG1) is regulated by eukaryotic initiation factor 3a (eIF3a) during cellular stress caused by iron depletion. PloS one 67 23437357
2008 An oncogenic role for the phosphorylated h-subunit of human translation initiation factor eIF3. The Journal of biological chemistry 67 18544531
1998 Characterization of cDNAs encoding the p44 and p35 subunits of human translation initiation factor eIF3. The Journal of biological chemistry 67 9822659
2016 A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism. Cell reports 64 27477275
2010 Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3. Structure (London, England : 1993) 64 20399188
2017 Human eIF3: from 'blobology' to biological insight. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 63 28138064
2002 The histone 3'-terminal stem-loop-binding protein enhances translation through a functional and physical interaction with eukaryotic initiation factor 4G (eIF4G) and eIF3. Molecular and cellular biology 63 12391154
2013 EJC core component MLN51 interacts with eIF3 and activates translation. Proceedings of the National Academy of Sciences of the United States of America 62 23530232
1996 Conservation and diversity in the structure of translation initiation factor EIF3 from humans and yeast. Biochimie 62 9150866
1999 A 110-kilodalton subunit of translation initiation factor eIF3 and an associated 135-kilodalton protein are encoded by the Saccharomyces cerevisiae TIF32 and TIF31 genes. The Journal of biological chemistry 61 10358023
2007 Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis. Nucleic acids research 59 17287294
2007 Foot-and-mouth disease virus infection induces proteolytic cleavage of PTB, eIF3a,b, and PABP RNA-binding proteins. Virology 59 17445855
2009 A new plant protein interacts with eIF3 and 60S to enhance virus-activated translation re-initiation. The EMBO journal 58 19745810
1991 Eukaryotic initiation factors eIF-2 and eIF-3: interactions, structure and localization in ribosomal initiation complexes. Biochimie 58 1742346
2010 The translational regulator eIF3a: the tricky eIF3 subunit! Biochimica et biophysica acta 55 20647036
2004 Crystal structure of human eIF3k, the first structure of eIF3 subunits. The Journal of biological chemistry 55 15180986
2014 Human eukaryotic initiation factor 2 (eIF2)-GTP-Met-tRNAi ternary complex and eIF3 stabilize the 43 S preinitiation complex. The Journal of biological chemistry 54 25246524
2002 Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome. FEBS letters 53 12220626
2018 The function and clinical significance of eIF3 in cancer. Gene 51 29908282
1997 Identification of partners of TIF34, a component of the yeast eIF3 complex, required for cell proliferation and translation initiation. The EMBO journal 50 9362495
2020 eIF-Three to Tango: emerging functions of translation initiation factor eIF3 in protein synthesis and disease. Journal of molecular cell biology 47 32279082
2017 Does eIF3 promote reinitiation after translation of short upstream ORFs also in mammalian cells? RNA biology 47 28745933
2014 eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of translation initiation. Cellular oncology (Dordrecht, Netherlands) 47 25070653
2010 Regulation of protein synthesis and the role of eIF3 in cancer. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 46 20922269
2020 The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm. Cell research 45 32132673
2013 The translational factor eIF3f: the ambivalent eIF3 subunit. Cellular and molecular life sciences : CMLS 44 23354061
2007 Role of eIF3a (eIF3 p170) in intestinal cell differentiation and its association with early development. Differentiation; research in biological diversity 44 17381544
2016 Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion. Structure (London, England : 1993) 41 27210288
2004 Eucaryotic initiation factor 4B controls eIF3-mediated ribosomal entry of viral reinitiation factor. The EMBO journal 41 14988734
2015 eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation. Oncotarget 38 26213845
1999 The Saccharomyces cerevisiae HCR1 gene encoding a homologue of the p35 subunit of human translation initiation factor 3 (eIF3) is a high copy suppressor of a temperature-sensitive mutation in the Rpg1p subunit of yeast eIF3. The Journal of biological chemistry 38 10488093
1999 Activity-dependent interaction of the intracellular domain of rat trkA with intermediate filament proteins, the beta-6 proteasomal subunit, Ras-GRF1, and the p162 subunit of eIF3. Journal of molecular neuroscience : MN 38 10691301
2022 YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer. ACS chemical biology 37 35708211
2014 The translation initiation complex eIF3 in trypanosomatids and other pathogenic excavates--identification of conserved and divergent features based on orthologue analysis. BMC genomics 35 25539953
2014 Topological models of heteromeric protein assemblies from mass spectrometry: application to the yeast eIF3:eIF5 complex. Chemistry & biology 35 25544043
2014 Structural integrity of the PCI domain of eIF3a/TIF32 is required for mRNA recruitment to the 43S pre-initiation complexes. Nucleic acids research 34 24423867
2013 Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a. Carcinogenesis 34 23393223
2001 Saccharomyces cerevisiae protein Pci8p and human protein eIF3e/Int-6 interact with the eIF3 core complex by binding to cognate eIF3b subunits. The Journal of biological chemistry 34 11457827
2017 Maternal Dead-end 1 promotes translation of nanos1 by binding the eIF3 complex. Development (Cambridge, England) 32 28870987
2012 Small ribosomal protein RPS0 stimulates translation initiation by mediating 40S-binding of eIF3 via its direct contact with the eIF3a/TIF32 subunit. PloS one 32 22792338
2016 Cellular mRNA recruits the ribosome via eIF3-PABP bridge to initiate internal translation. RNA biology 31 26828225
2007 Benzo(a)pyrene inhibits growth and functional differentiation of mouse bone marrow-derived dendritic cells. Downregulation of RelB and eIF3 p170 by benzo(a)pyrene. Toxicology letters 31 17275222
2019 Repression of ferritin light chain translation by human eIF3. eLife 30 31414986
2013 The m subunit of murine translation initiation factor eIF3 maintains the integrity of the eIF3 complex and is required for embryonic development, homeostasis, and organ size control. The Journal of biological chemistry 29 24003236
1999 Cloning and characterization of the p42 subunit of mammalian translation initiation factor 3 (eIF3): demonstration that eIF3 interacts with eIF5 in mammalian cells. Nucleic acids research 29 9973622
2021 Robust T cell activation requires an eIF3-driven burst in T cell receptor translation. eLife 28 34970966
2000 Protein 4.1R binding to eIF3-p44 suggests an interaction between the cytoskeletal network and the translation apparatus. Blood 28 10887144
2015 The eIF3 complex of Leishmania-subunit composition and mode of recruitment to different cap-binding complexes. Nucleic acids research 27 26092695
2019 Serum anti-EIF3A autoantibody as a potential diagnostic marker for hepatocellular carcinoma. Scientific reports 26 31363116
2021 eIF3a R803K mutation mediates chemotherapy resistance by inducing cellular senescence in small cell lung cancer. Pharmacological research 25 34648968
2020 Structure of the RNA Specialized Translation Initiation Element that Recruits eIF3 to the 5'-UTR of c-Jun. Journal of molecular biology 25 31953146
2018 Eukaryotic translation initiation factor 3 (eIF3) subunit e is essential for embryonic development and cell proliferation. FEBS open bio 25 30087825
2012 The A/G allele of eIF3a rs3740556 predicts platinum-based chemotherapy resistance in lung cancer patients. Lung cancer (Amsterdam, Netherlands) 24 23127338
2000 Rpg1p, the subunit of the Saccharomyces cerevisiae eIF3 core complex, is a microtubule-interacting protein. Cell motility and the cytoskeleton 24 10706778
2015 Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients. Acta pharmacologica Sinica 23 25732572
2012 Overexpression of eIF3a in Squamous Cell Carcinoma of the Oral Cavity and Its Putative Relation to Chemotherapy Response. Journal of oncology 23 22619676
2001 Two subcellular localizations of eIF3 p170 and its interaction with membrane-bound microfilaments: implications for alternative functions of p170. European journal of cell biology 23 11484932
2019 eIF3a mediates HIF1α-dependent glycolytic metabolism in hepatocellular carcinoma cells through translational regulation. American journal of cancer research 22 31218114

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