Affinage

EIF3J

Eukaryotic translation initiation factor 3 subunit J · UniProt O75822

Length
258 aa
Mass
29.1 kDa
Annotated
2026-06-09
19 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF3J encodes a peripherally associated subunit of the eIF3 complex that occupies the decoding center of the small ribosomal subunit and acts as a regulatory hub across multiple steps of the translation cycle (PMID:17588516, PMID:25664723). It binds directly within the aminoacyl (A) site and mRNA entry channel of the 40S subunit, where it contacts eIF1A and lowers the affinity of the 40S for mRNA; this affinity is restored upon initiator-tRNA recruitment, positioning eIF3j as a gatekeeper of the mRNA-binding cleft during initiation (PMID:17588516, PMID:25664723). Its N-terminal acidic motif anchors a conserved tryptophan into a hydrophobic pocket of the eIF3b RNA-recognition motif, an interaction required to recruit the eIF3b-RRM to the 40S and to support stringent AUG selection during scanning; together with the eIF3a C-terminal domain near the mRNA entry channel, this module governs the transition between scanning-conducive and initiation-competent preinitiation-complex conformations (PMID:17190833, PMID:20060839, PMID:20584985). Stable incorporation of eIF3j into eIF3 requires CK2-mediated phosphorylation at Ser127, and loss of this modification disrupts complex assembly and reduces global protein synthesis (PMID:25887626). Beyond initiation, eIF3j promotes translation termination by facilitating loading of the eRF1–eRF3 release-factor complex into the A-site prior to GTP hydrolysis, and assists post-termination ribosome recycling, with the yeast ortholog Hcr1 specifically required for 60S subunit recycling (PMID:31269449, PMID:34591963). The yeast protein additionally functions in late cytoplasmic 40S biogenesis, enhancing 20S pre-rRNA processing to 18S rRNA (PMID:11560931), and the Drosophila ortholog represses cap-independent translation of a circular RNA by displacing eIF3 from the transcript during the heat-shock response (PMID:36330957).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2001 High

    Established eIF3j/Hcr1 as more than a passive eIF3 subunit by showing it binds RNA, stabilizes the multifactor initiation complex, and is required for late cytoplasmic 40S ribosome maturation, linking the protein to both initiation and subunit biogenesis.

    Evidence Yeast deletion/synthetic lethality genetics, immunofluorescence, co-IP, and Northern blots of 20S pre-rRNA in yeast with human ortholog tested for complementation

    PMID:11560931

    Open questions at the time
    • Human p35/eIF3j failed to complement the yeast 40S biogenesis defect, leaving the conservation of the biogenesis role unresolved
    • Mechanism coupling multifactor-complex stabilization to pre-rRNA processing not defined
  2. 2006 High

    Mapped the physical basis of eIF3j–eIF3b coupling by showing the eIF3j N-terminal 69-residue peptide binds the eIF3b-RRM and is essential for recruiting the RRM to the 40S, defining how eIF3j anchors part of the eIF3 core to the ribosome.

    Evidence NMR solution structure of eIF3b-RRM plus peptide binding and 40S recruitment assays

    PMID:17190833

    Open questions at the time
    • Functional consequence of the interaction for scanning or AUG selection not yet tested
    • Did not address eIF3j contacts with the ribosome itself
  3. 2007 High

    Located eIF3j at the ribosomal decoding center and revealed its gatekeeper logic, showing it occupies the A-site and mRNA entry channel, lowers 40S–mRNA affinity, contacts eIF1A, and responds to initiator-tRNA recruitment.

    Evidence Directed hydroxyl radical probing of human 40S complexes with multiple functional readouts

    PMID:17588516

    Open questions at the time
    • Did not resolve how cleft access is communicated to downstream scanning
    • Static probing rather than dynamic measurement of the conformational transition
  4. 2010 Medium

    Connected the eIF3j–eIF3b–eIF3a module structurally and genetically to AUG selection fidelity, demonstrating that a conserved tryptophan anchors eIF3j to the eIF3b-RRM and that disrupting it causes leaky scanning suppressible by eIF1A overexpression.

    Evidence NMR structure of the NTA–RRM interface, yeast mutagenesis with leaky-scanning reporters, co-IP, and in vitro binding (two complementary studies)

    PMID:20060839 PMID:20584985

    Open questions at the time
    • The eIF3a-CTD contributions rest on single-lab genetic epistasis plus co-IP
    • How the module toggles between scanning and initiation-competent conformations not directly visualized
  5. 2015 High

    Provided a structural snapshot of eIF3j in an assembled initiation complex and identified the regulatory switch controlling its incorporation, showing direct eIF3j–eIF1A contact by cryo-EM and that CK2 phosphorylation at Ser127 is required for eIF3 assembly and global translation.

    Evidence Cryo-EM of a yeast 40S–eIF1–eIF1A–eIF3–eIF3j complex; and CK2 inhibitor/knockdown, mass spectrometry, Ser127Ala mutagenesis, and protein-synthesis assays (two studies)

    PMID:25664723 PMID:25887626

    Open questions at the time
    • Cryo-EM noted differences between yeast and mammalian eIF3 binding that were not fully reconciled
    • Upstream signals controlling CK2-dependent eIF3j phosphorylation unknown
  6. 2019 High

    Extended eIF3j function beyond initiation to ribosome recycling, showing in yeast that loss of Hcr1 causes AUG-independent 3'UTR reinitiation attributable to a 60S (not 40S) recycling defect, suppressed by Rli1/ABCE1 overexpression.

    Evidence Genome-wide ribosome profiling, reporter assays, and overexpression/deletion epistasis in yeast

    PMID:31269449

    Open questions at the time
    • Molecular mechanism by which eIF3j assists 60S recycling not defined
    • Conservation of the recycling role in mammals not tested here
  7. 2021 High

    Defined a direct role for human eIF3j in translation termination, showing it stimulates eRF1–eRF3-induced peptidyl-tRNA hydrolysis by acting at the release-factor loading step prior to GTP hydrolysis.

    Evidence Reconstituted mammalian in vitro translation, peptide-release and toe-printing assays, and pull-downs with eRF1, eRF3, and PABP

    PMID:34591963

    Open questions at the time
    • Structural basis of eIF3j positioning during termination not resolved
    • Relationship between the termination role and the 60S recycling role not integrated
  8. 2022 Medium

    Revealed a repressive role for eIF3j in cap-independent circular RNA translation, showing that in Drosophila it displaces eIF3 from circSfl via its C-terminus and a UTR RNA regulon, with physiological relevance during heat shock.

    Evidence Drosophila eIF screen, circRNA translation reporters, domain mutagenesis, and in vivo heat-shock experiments

    PMID:36330957

    Open questions at the time
    • Single-lab study in Drosophila; conservation of circRNA repression in mammals untested
    • How eIF3j discriminates circRNA from canonical mRNA substrates unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How eIF3j's distinct roles across initiation gatekeeping, AUG fidelity, termination, ribosome recycling, and circRNA repression are coordinated within a single cell remains unresolved.
  • No unified structural model spanning initiation, termination, and recycling states
  • Regulatory inputs (beyond CK2) that partition eIF3j among these functions unknown
  • Mammalian relevance of the yeast biogenesis and recycling roles not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 4 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1
Localization
GO:0005840 ribosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 3
Partners
EIF1AXEIF3AEIF3BERF1ERF3PABPC1RPS2RPS23
Complex memberships
43S preinitiation complexeIF3multifactor complex (eIF1/eIF2/eIF3/eIF5/Met-tRNA)

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Human eIF3j binds directly to the aminoacyl (A) site and mRNA entry channel of the 40S ribosomal subunit (decoding center), interacts with eIF1A, reduces 40S affinity for mRNA, and this affinity is restored upon recruitment of initiator tRNA even while eIF3j remains in the mRNA-binding cleft, indicating eIF3j regulates access of the mRNA-binding cleft in response to initiation factor binding. Directed hydroxyl radical probing of human 40S ribosomal subunit complexes Molecular cell High 17588516
2006 The N-terminal 69-amino acid peptide of human eIF3j binds specifically to the rear alpha-helices of the eIF3b RNA recognition motif (RRM), and this interaction is essential for eIF3b-RRM recruitment to the 40S ribosomal subunit. NMR solution structure of eIF3b-RRM; binding assays identifying eIF3j N-terminal peptide as sufficient for eIF3b-RRM interaction and 40S recruitment The Journal of biological chemistry High 17190833
2010 A conserved tryptophan in the human eIF3j N-terminal acidic motif (NTA) is held in the helix α1/loop 5 hydrophobic pocket of the human eIF3b RRM. Mutating the corresponding yeast residues eliminates eIF3j/HCR1 association with eIF3b/PRT1 in vitro and in vivo, reduces 40S occupancy of eIF3, and produces a leaky scanning (AUG selection) defect partially suppressed by overexpressed eIF1A. eIF3j/HCR1 was found to interact with small ribosomal proteins RPS2 and RPS23 near the mRNA entry channel. NMR spectroscopy (solution structure of eIF3j NTA–eIF3b RRM interaction); yeast genetics (growth assays, leaky scanning reporter); co-immunoprecipitation; in vitro binding assays Journal of molecular biology High 20060839
2010 The C-terminal domain (CTD) of yeast eIF3a/Tif32 interacts with eIF3j/HCR1 and eIF3b/Prt1, and the eIF3j/HCR1 CTD is required for its binding to eIF3a. The eIF3b-RRM–eIF3j/HCR1–eIF3a-CTD module functions near the mRNA entry channel to regulate the transition between scanning-conducive and initiation-competent conformations of the preinitiation complex (PIC), and the eIF3a CTD binds ribosomal proteins Rps2 and Rps3. Yeast genetic analysis (substitution mutants, growth phenotypes, leaky scanning assays); co-immunoprecipitation; in vitro binding assays Molecular and cellular biology Medium 20584985
2001 Yeast eIF3j/Hcr1p is an RNA-binding protein that (1) binds to and stabilizes the multifactor complex (eIFs 1, 2, 3, 5 + Met-tRNA), (2) enhances a late cytoplasmic step in 40S ribosome maturation (20S pre-rRNA to 18S rRNA processing), and (3) its deletion causes decreased 40S subunits, paromomycin hypersensitivity, and synthetic lethality with drs2Δ or rps0aΔ. Human p35/eIF3j associates with yeast eIF3 and 43S initiation complexes in vitro and in vivo but does not complement the 40S biogenesis defect of hcr1Δ. Yeast genetics (deletion analysis, synthetic lethality, complementation); immunofluorescence localization; in vitro and in vivo co-immunoprecipitation; Northern blot (20S pre-rRNA accumulation) The Journal of biological chemistry High 11560931
2015 Cryo-EM structure of a yeast 40S–eIF1–eIF1A–eIF3–eIF3j initiation complex reveals that eIF3j makes direct contact with eIF1A and shows the network of interactions among eIF3 subunits, with differences in initiation-complex binding compared to mammalian eIF3. Cryo-electron microscopy with placement of prior X-ray/NMR structures Nature structural & molecular biology High 25664723
2015 Protein kinase CK2 interacts with eIF3j and phosphorylates it at Ser127. Inhibition or knockdown of CK2 causes dissociation of eIF3j from the eIF3 complex. Expression of the Ser127Ala mutant impairs eIF3j association with other eIF3 subunits and reduces overall protein synthesis, demonstrating that CK2-mediated phosphorylation of eIF3j at Ser127 is required for eIF3 complex assembly and translation initiation. Co-immunoprecipitation; mass spectrometry; glycerol gradient sedimentation; CK2 inhibitor (CX-4945) and siRNA knockdown; Ser127Ala mutagenesis; protein synthesis assay Biochimica et biophysica acta High 25887626
2019 In yeast, loss of Hcr1/eIF3j leads to reinitiation of translation in 3′ UTRs consistent with a recycling defect; the defect is in 60S subunit recycling (not 40S), because reinitiation does not require an AUG codon and is suppressed by overexpression of the 60S dissociation factor Rli1/ABCE1. Hcr1 overexpression cannot compensate for loss of 40S recycling factors Tma64/eIF2D and Tma20/MCT-1, and loss of Hcr1 triggers increased RLI1 expression via an apparent feedback loop. Ribosome profiling (genome-wide); reporter translation assays; genetic overexpression/deletion epistasis in yeast Cell reports High 31269449
2021 Human eIF3j stimulates peptidyl-tRNA hydrolysis induced by the eRF1–eRF3 release factor complex in a reconstituted mammalian in vitro translation system. eIF3j activity in termination is enhanced by co-presence of the eIF3 complex. eIF3j interacts with the pre-termination ribosomal complex, and eRF3 destabilizes this interaction. In solution, eIF3j binds eRF1, eRF3, and PABP in the presence of GTP. Toe-printing established that eIF3j acts at the step of release factor loading into the A-site, before GTP hydrolysis. Reconstituted mammalian in vitro translation system; peptide release assay; toe-printing assay; pull-down binding assays Nucleic acids research High 34591963
2022 Drosophila eIF3j (the eIF3-associated factor) inhibits translation of the circular RNA circSfl. Mechanistically, eIF3j binding to circSfl promotes dissociation of the eIF3 complex from the circRNA. The C-terminus of eIF3j and an RNA regulon within the circSfl UTR are essential for this inhibitory effect. eIF3j-mediated circRNA translation repression is physiologically relevant during heat shock response. Drosophila eIF3j screen (all 43 eIFs tested); circRNA translation reporter assays; domain deletion/mutagenesis; in vivo heat shock experiments Nucleic acids research Medium 36330957

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Long noncoding RNA (lncRNA) EIF3J-DT induces chemoresistance of gastric cancer via autophagy activation. Autophagy 197 33764843
2007 eIF3j is located in the decoding center of the human 40S ribosomal subunit. Molecular cell 108 17588516
2015 Structure of a yeast 40S-eIF1-eIF1A-eIF3-eIF3j initiation complex. Nature structural & molecular biology 84 25664723
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
2010 The indispensable N-terminal half of eIF3j/HCR1 cooperates with its structurally conserved binding partner eIF3b/PRT1-RRM and with eIF1A in stringent AUG selection. Journal of molecular biology 76 20060839
2001 Dual function of eIF3j/Hcr1p in processing 20 S pre-rRNA and translation initiation. The Journal of biological chemistry 56 11560931
2006 Structure of eIF3b RNA recognition motif and its interaction with eIF3j: structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit. The Journal of biological chemistry 55 17190833
2019 Hypoxia-induced lncRNA EIF3J-AS1 accelerates hepatocellular carcinoma progression via targeting miR-122-5p/CTNND2 axis. Biochemical and biophysical research communications 40 31421822
2019 Hcr1/eIF3j Is a 60S Ribosomal Subunit Recycling Accessory Factor In Vivo. Cell reports 38 31269449
2019 H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through miR-3163/YAP1 axis. Journal of cellular biochemistry 35 31709617
2022 eIF3j inhibits translation of a subset of circular RNAs in eukaryotic cells. Nucleic acids research 31 36330957
2020 LncRNA EIF3J-AS1 enhanced esophageal cancer invasion via regulating AKT1 expression through sponging miR-373-3p. Scientific reports 20 32811869
2021 eIF3j facilitates loading of release factors into the ribosome. Nucleic acids research 17 34591963
2015 Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127. Biochimica et biophysica acta 14 25887626
2020 EIF3J-AS1 promotes glioma cell growth via up-regulating ANXA11 through sponging miR-1343-3p. Cancer cell international 10 32905397
2024 LncRNA EIF3J-DT promotes chemoresistance in oral squamous cell carcinoma. Oral diseases 5 38817073
2022 LncRNA EIF3J-AS1 functions as an oncogene by regulating MAFG to promote prostate cancer progression. Journal of Cancer 3 34976178
2026 Deletion of the translation initiation factor eIF3j promotes the synthesis of amylase and kojic acid in the fungus Aspergillus oryzae. Mycologia 0 42118908
2025 miR-101/METTL3 axis induces autophagy by interrupting FOXG1/EIF3J-AS1 binding in gliomas. Cell death & disease 0 41390674

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