{"gene":"ZNF346","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":1999,"finding":"ZNF346 (JAZ) contains four C2H2-type zinc finger motifs connected by long linker sequences and preferentially binds double-stranded RNA (dsRNA) or RNA/DNA hybrids rather than DNA. The zinc finger domains are required both for dsRNA binding and for nucleolar localization. Forced expression of ZNF346 potently induces apoptosis in murine fibroblast cells.","method":"Cloning and characterization; mutagenesis of individual zinc finger motifs; subcellular localization; overexpression apoptosis assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct mutagenesis linking zinc finger domains to both dsRNA binding and nuclear localization, with functional apoptosis readout; single lab but multiple orthogonal methods","pmids":["10488071"],"is_preprint":false},{"year":2004,"finding":"ZNF346 (JAZ) is a cargo protein for exportin-5 and undergoes nucleocytoplasmic shuttling. JAZ binds exportin-5 in a Ran-GTP- and dsRNA-dependent manner; exportin-5 stimulates JAZ nuclear export, and gene silencing of exportin-5 reduces shuttling. JAZ also binds ILF3 in an RNA-independent manner requiring the dsRNA-binding domains of ILF3, and JAZ, ILF3, and exportin-5 can form a heteromeric complex with Ran-GTP and dsRNA. Nuclear import of JAZ does not require energy or cytosol but is blocked by low temperature, suggesting facilitated diffusion.","method":"Co-immunoprecipitation; permeabilized cell nuclear export assay; siRNA knockdown of exportin-5; Ran-GTP binding assay; nucleocytoplasmic shuttling assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal binding assays, siRNA knockdown, permeabilized cell reconstitution, and multiple orthogonal methods establishing the export mechanism","pmids":["15254228"],"is_preprint":false},{"year":2006,"finding":"ZNF346 (JAZ) physically associates with p53 and stimulates p53 transcriptional activity, mediating G1 cell-cycle arrest and apoptosis in a p53-dependent mechanism involving upregulation of p21 and BAX, dephosphorylation of Rb, and repression of cyclin A. The interaction requires p53's C-terminal regulatory domain but is independent of dsRNA. The dsRNA-binding zinc finger domains are required for nuclear localization and for stimulatory activity in vivo. siRNA knockdown of endogenous ZNF346 inhibits p53 transcriptional activity, decreases the G1/G0 population, and attenuates stress-induced cell death.","method":"Co-immunoprecipitation; in vitro binding assay; reporter assays; siRNA knockdown; flow cytometry cell cycle analysis; p53-null cell complementation","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vitro direct binding plus siRNA loss-of-function with specific cell cycle/apoptosis phenotypes, p53-null complementation, multiple orthogonal methods in single study","pmids":["16931621"],"is_preprint":false},{"year":2011,"finding":"ZNF346 (JAZ) directly interacts with E2F1, associating with E2F1's central DNA binding/dimerization region and its C-terminal transactivation domain. ZNF346 represses E2F1 transcriptional activity, inhibits E2F1's specific DNA binding activity, represses cyclin A expression, and inhibits G1/S transition. This mechanism is independent of p53. siRNA knockdown of endogenous ZNF346 increases E2F transcriptional activity and releases cells from G1 arrest.","method":"Co-immunoprecipitation; in vitro direct binding assay; reporter assays; siRNA knockdown; cell cycle analysis","journal":"Cell cycle (Georgetown, Tex.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vitro direct binding, siRNA loss-of-function with specific transcriptional and cell cycle phenotypes, domain mapping, multiple orthogonal methods","pmids":["21715977"],"is_preprint":false},{"year":2014,"finding":"ZNF346 (JAZ) preferentially binds dsRNA with no detectable sequence specificity; affinity is unaffected by local structural features (loops, overhangs, bulges) provided sufficient A-form RNA (~18 bp per zinc finger) is present. Full-length JAZ with all four C2H2 zinc fingers (ZF1-4) has the highest dsRNA affinity; two-finger constructs ZF12 and ZF23 have lower affinity; ZF34 binds more weakly; ZF4 alone has no measurable RNA-binding affinity. Quantitative NMR and ITC data fitted to a two-site binding model yielded Kd1 ~10 μM and Kd2 ~100 μM. HADDOCK-generated models indicate single zinc fingers bind the RNA backbone without sequence specificity via contacts between the RNA minor groove and N-terminal β strands and the major groove and helix-kink-helix motif residues.","method":"Electrophoretic mobility shift assays (EMSA); isothermal titration calorimetry (ITC); nuclear magnetic resonance (NMR) spectroscopy; HADDOCK computational docking","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — quantitative in vitro binding (ITC + NMR + EMSA) with domain-deletion series and structural modeling; multiple orthogonal methods in a single rigorous study","pmids":["24521053"],"is_preprint":false},{"year":2018,"finding":"miR-1247 directly targets the 3′UTR of ZNF346 mRNA in neuroblastoma cells, repressing ZNF346 protein expression. siRNA-mediated knockdown of ZNF346 suppresses neuroblastoma cell proliferation, induces G0/G1 cell cycle arrest, and promotes apoptosis, phenocopying miR-1247 overexpression.","method":"Luciferase reporter assay (3′UTR targeting); siRNA knockdown; MTT assay; colony formation assay; flow cytometry; Western blotting","journal":"Biological research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct 3′UTR luciferase validation of miR-1247 targeting ZNF346, siRNA knockdown phenocopying miR-1247 overexpression; single lab with two orthogonal methods","pmids":["29793538"],"is_preprint":false},{"year":2020,"finding":"miR-542-3p reduces ZNF346 protein levels in neuroblastoma cells through direct interaction, and ZNF346 upregulation weakens the anti-proliferative and anti-invasive effects of miR-542-3p, indicating that ZNF346 is a functional downstream target mediating miR-542-3p's tumor-suppressive activity.","method":"miR-542-3p overexpression; Western blotting for ZNF346; ZNF346 rescue overexpression; cell proliferation and invasion assays; in vivo tumor growth assay","journal":"Open life sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, no direct 3′UTR luciferase validation for ZNF346 reported; rescue experiment supports functional link but limited mechanistic detail","pmids":["33987474"],"is_preprint":false}],"current_model":"ZNF346 (JAZ) is a nucleolar C2H2-type zinc finger protein that preferentially binds double-stranded RNA in a sequence-nonspecific manner through its first three zinc fingers; it shuttles between nucleus and cytoplasm via exportin-5 in a Ran-GTP/dsRNA-dependent export mechanism with facilitated diffusion re-entry, forms a complex with ILF3, acts as a positive regulator of p53 transcriptional activity by directly binding p53's C-terminal domain to mediate G1 arrest and apoptosis, and independently represses cell proliferation by directly binding and inhibiting E2F1 transcriptional and DNA-binding activity, thereby providing dual p53-dependent and p53-independent mechanisms of cell-cycle control."},"narrative":{"mechanistic_narrative":"ZNF346 (JAZ) is a nucleolar C2H2-type zinc finger protein that functions as a double-stranded RNA-binding regulator of cell-cycle progression and apoptosis [PMID:10488071, PMID:16931621]. Its four zinc fingers, connected by long linkers, preferentially bind A-form dsRNA or RNA/DNA hybrids in a sequence-nonspecific manner, with the full-length four-finger array providing maximal affinity and the same zinc finger domains being required for nucleolar localization [PMID:10488071, PMID:24521053]. ZNF346 is an exportin-5 cargo that shuttles between nucleus and cytoplasm in a Ran-GTP- and dsRNA-dependent manner, re-entering the nucleus by facilitated diffusion, and it assembles with ILF3 and exportin-5 into a heteromeric Ran-GTP/dsRNA complex [PMID:15254228]. Functionally, ZNF346 exerts dual control over the G1/S transition: it physically associates with the C-terminal regulatory domain of p53 to stimulate p53 transcriptional activity, driving p21 and BAX upregulation, Rb dephosphorylation, cyclin A repression, G1 arrest, and apoptosis [PMID:16931621], and in a p53-independent arm it directly binds E2F1, inhibiting E2F1 DNA binding and transactivation to repress cyclin A and block G1/S progression [PMID:21715977]. Consistent with this anti-proliferative role, ZNF346 is a target of tumor-suppressive microRNAs in neuroblastoma, where its loss suppresses proliferation and promotes apoptosis [PMID:29793538].","teleology":[{"year":1999,"claim":"Established that ZNF346 is a zinc finger protein with an unexpected nucleic-acid preference, defining it as a dsRNA-binding rather than DNA-binding protein and linking it to apoptosis.","evidence":"Cloning, zinc finger mutagenesis, subcellular localization, and overexpression apoptosis assay in murine fibroblasts","pmids":["10488071"],"confidence":"Medium","gaps":["Did not identify physiological dsRNA targets or binding partners","Mechanism linking dsRNA binding to apoptosis not resolved"]},{"year":2004,"claim":"Resolved how ZNF346 moves between compartments, defining it as an exportin-5 cargo and identifying ILF3 as a stable partner in a Ran-GTP/dsRNA complex.","evidence":"Co-immunoprecipitation, permeabilized-cell nuclear export assay, exportin-5 siRNA knockdown, and Ran-GTP binding assay","pmids":["15254228"],"confidence":"High","gaps":["Functional consequence of nucleocytoplasmic shuttling for downstream signaling not established","Cargo carried by ZNF346 during export not identified"]},{"year":2006,"claim":"Defined the first regulatory output of ZNF346, showing it is a positive cofactor for p53 that drives p53-dependent G1 arrest and apoptosis.","evidence":"Co-IP, in vitro binding, reporter assays, siRNA knockdown, flow cytometry, and p53-null complementation","pmids":["16931621"],"confidence":"High","gaps":["Structural basis of the p53 C-terminal interaction not determined","Whether dsRNA binding modulates p53 cofactor activity not resolved"]},{"year":2011,"claim":"Showed ZNF346 acts through a second, p53-independent route by directly binding and inhibiting E2F1, establishing dual mechanisms of cell-cycle control.","evidence":"Co-IP, in vitro direct binding, domain mapping, reporter assays, siRNA knockdown, and cell cycle analysis","pmids":["21715977"],"confidence":"High","gaps":["Relative contribution of p53 vs E2F1 arms in vivo not quantified","How the two activities are coordinated unknown"]},{"year":2014,"claim":"Provided the quantitative and structural basis for dsRNA recognition, defining affinity contributions of individual zinc fingers and the sequence-nonspecific A-form recognition mode.","evidence":"EMSA, ITC, NMR, and HADDOCK docking with domain-deletion constructs","pmids":["24521053"],"confidence":"High","gaps":["No experimental high-resolution complex structure","Physiological dsRNA ligands and how RNA binding integrates with transcriptional regulation not addressed"]},{"year":2020,"claim":"Placed ZNF346 in a tumor context as a proliferation-promoting target of regulatory microRNAs, contrasting with its anti-proliferative biochemical activities.","evidence":"miR-1247 3'UTR luciferase validation and siRNA knockdown (2018); miR-542-3p overexpression with ZNF346 rescue and in vivo tumor assays (2020)","pmids":["29793538","33987474"],"confidence":"Medium","gaps":["miR-542-3p targeting of ZNF346 lacks direct 3'UTR luciferase validation","How a p53/E2F1 cell-cycle regulator promotes neuroblastoma proliferation mechanistically unresolved"]},{"year":null,"claim":"How ZNF346's dsRNA binding, exportin-5 shuttling, and ILF3 association mechanistically connect to its p53/E2F1 transcriptional functions remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No identified endogenous dsRNA ligand linking RNA binding to transcriptional regulation","Physiological role of the ILF3/exportin-5 complex not defined","No structural model of the p53 or E2F1 complexes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,3]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1]}],"complexes":[],"partners":["ILF3","XPO5","TP53","E2F1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UL40","full_name":"Zinc finger protein 346","aliases":["Just another zinc finger protein"],"length_aa":294,"mass_kda":32.9,"function":"Binds with low affinity to dsDNA and ssRNA, and with high affinity to dsRNA, with no detectable sequence specificity (PubMed:24521053). May bind to specific miRNA hairpins (PubMed:28431233)","subcellular_location":"Nucleus, nucleolus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9UL40/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNF346","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DHX9","stoichiometry":0.2},{"gene":"EIF2AK2","stoichiometry":0.2},{"gene":"HNRNPD","stoichiometry":0.2},{"gene":"ILF3","stoichiometry":0.2},{"gene":"SNRPA","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ZNF346","total_profiled":1310},"omim":[{"mim_id":"618032","title":"ZINC FINGER PROTEIN 768; ZNF768","url":"https://www.omim.org/entry/618032"},{"mim_id":"605308","title":"ZINC FINGER PROTEIN 346; ZNF346","url":"https://www.omim.org/entry/605308"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZNF346"},"hgnc":{"alias_symbol":["JAZ","Zfp346"],"prev_symbol":[]},"alphafold":{"accession":"Q9UL40","domains":[{"cath_id":"3.30.160.60","chopping":"39-110","consensus_level":"high","plddt":80.7647,"start":39,"end":110},{"cath_id":"3.30.160.60","chopping":"187-224","consensus_level":"medium","plddt":81.8008,"start":187,"end":224}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UL40","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UL40-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UL40-F1-predicted_aligned_error_v6.png","plddt_mean":66.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNF346","jax_strain_url":"https://www.jax.org/strain/search?query=ZNF346"},"sequence":{"accession":"Q9UL40","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UL40.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UL40/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UL40"}},"corpus_meta":[{"pmid":"17637677","id":"PMC_17637677","title":"JAZ 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behavior","url":"https://pubmed.ncbi.nlm.nih.gov/24394987","citation_count":21,"is_preprint":false},{"pmid":"34716392","id":"PMC_34716392","title":"Genome-wide identification and expression analysis of the JAZ gene family in turnip.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/34716392","citation_count":20,"is_preprint":false},{"pmid":"35217668","id":"PMC_35217668","title":"Genome-wide characterization of the sorghum JAZ gene family and their responses to phytohormone treatments and aphid infestation.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/35217668","citation_count":20,"is_preprint":false},{"pmid":"35236292","id":"PMC_35236292","title":"Genome-wide analysis of JAZ family genes expression patterns during fig (Ficus carica L.) fruit development and in response to hormone treatment.","date":"2022","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35236292","citation_count":19,"is_preprint":false},{"pmid":"30728246","id":"PMC_30728246","title":"A comprehensive in vitro fluorescence anisotropy assay system for screening ligands of the jasmonate COI1-JAZ co-receptor in plants.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30728246","citation_count":19,"is_preprint":false},{"pmid":"37322867","id":"PMC_37322867","title":"Assembly of JAZ-JAZ and JAZ-NINJA complexes in jasmonate signaling.","date":"2023","source":"Plant communications","url":"https://pubmed.ncbi.nlm.nih.gov/37322867","citation_count":18,"is_preprint":false},{"pmid":"37834452","id":"PMC_37834452","title":"An Investigation of the JAZ Family and the CwMYC2-like Protein to Reveal Their Regulation Roles in the MeJA-Induced Biosynthesis of β-Elemene in Curcuma wenyujin.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37834452","citation_count":18,"is_preprint":false},{"pmid":"16931621","id":"PMC_16931621","title":"JAZ mediates G1 cell-cycle arrest and apoptosis by positively regulating p53 transcriptional activity.","date":"2006","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/16931621","citation_count":18,"is_preprint":false},{"pmid":"31118943","id":"PMC_31118943","title":"Genome-Wide Identification and Characterization of the JAZ Gene Family in Rubber Tree (Hevea brasiliensis).","date":"2019","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31118943","citation_count":17,"is_preprint":false},{"pmid":"24521053","id":"PMC_24521053","title":"Structural characterization of interactions between the double-stranded RNA-binding zinc finger protein JAZ and nucleic acids.","date":"2014","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24521053","citation_count":17,"is_preprint":false},{"pmid":"25008776","id":"PMC_25008776","title":"Synthesis of 6-substituted 1-oxoindanoyl isoleucine conjugates and modeling studies with the COI1-JAZ co-receptor complex of lima bean.","date":"2014","source":"Journal of chemical ecology","url":"https://pubmed.ncbi.nlm.nih.gov/25008776","citation_count":17,"is_preprint":false},{"pmid":"34193940","id":"PMC_34193940","title":"Extended JAZ degron sequence for plant hormone binding in jasmonate co-receptor of tomato SlCOI1-SlJAZ.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/34193940","citation_count":13,"is_preprint":false},{"pmid":"37047679","id":"PMC_37047679","title":"Genome-Wide Identification and Analysis Uncovers the Potential Role of JAZ and MYC Families in Potato under Abiotic Stress.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37047679","citation_count":13,"is_preprint":false},{"pmid":"38558522","id":"PMC_38558522","title":"A signaling cascade mediating fruit trait development via phosphorylation-modulated nuclear accumulation of JAZ repressor.","date":"2024","source":"Journal of integrative plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/38558522","citation_count":13,"is_preprint":false},{"pmid":"32647129","id":"PMC_32647129","title":"A new functional JAZ degron sequence in strawberry JAZ1 revealed by structural and interaction studies on the COI1-JA-Ile/COR-JAZs complexes.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32647129","citation_count":13,"is_preprint":false},{"pmid":"34982368","id":"PMC_34982368","title":"Key Genes in the JAZ Signaling Pathway Are Up-Regulated Faster and More Abundantly in Caterpillar-Resistant Maize.","date":"2022","source":"Journal of chemical ecology","url":"https://pubmed.ncbi.nlm.nih.gov/34982368","citation_count":12,"is_preprint":false},{"pmid":"32182273","id":"PMC_32182273","title":"Identification, molecular characterization and expression of JAZ genes in Lycoris aurea.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32182273","citation_count":11,"is_preprint":false},{"pmid":"34445565","id":"PMC_34445565","title":"Transcriptome-Wide Identification and Characterization of the JAZ Gene Family in Mentha canadensis L.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34445565","citation_count":11,"is_preprint":false},{"pmid":"23989667","id":"PMC_23989667","title":"RICE SALT SENSITIVE3 binding to bHLH and JAZ factors mediates control of cell wall plasticity in the root apex.","date":"2013","source":"Plant signaling & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/23989667","citation_count":11,"is_preprint":false},{"pmid":"29343866","id":"PMC_29343866","title":"Identification of JAZ-interacting MYC transcription factors involved in latex drainage in Hevea brasiliensis.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29343866","citation_count":11,"is_preprint":false},{"pmid":"31277246","id":"PMC_31277246","title":"Genome-Wide Identification and Characterization of JAZ Protein Family in Two Petunia Progenitors.","date":"2019","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31277246","citation_count":10,"is_preprint":false},{"pmid":"26460857","id":"PMC_26460857","title":"A JAZ Protein in Astragalus sinicus Interacts with a Leghemoglobin through the TIFY Domain and Is Involved in Nodule Development and Nitrogen Fixation.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26460857","citation_count":10,"is_preprint":false},{"pmid":"34575953","id":"PMC_34575953","title":"Genome-Wide Identification and Expression Analysis of JAZ Family Involved in Hormone and Abiotic Stress in Sweet Potato and Its Two Diploid Relatives.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34575953","citation_count":10,"is_preprint":false},{"pmid":"32043408","id":"PMC_32043408","title":"JA modulates phytochrome a signaling via repressing FHY3 activity by JAZ proteins.","date":"2020","source":"Plant signaling & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/32043408","citation_count":10,"is_preprint":false},{"pmid":"38579542","id":"PMC_38579542","title":"Genome-wide identification of JAZ gene family in sugarcane and function analysis of ScJAZ1/2 in drought stress response and flowering regulation.","date":"2024","source":"Plant physiology and biochemistry : PPB","url":"https://pubmed.ncbi.nlm.nih.gov/38579542","citation_count":9,"is_preprint":false},{"pmid":"32973821","id":"PMC_32973821","title":"The Molecular Basis of JAZ-MYC Coupling, a Protein-Protein Interface Essential for Plant Response to Stressors.","date":"2020","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/32973821","citation_count":9,"is_preprint":false},{"pmid":"36096884","id":"PMC_36096884","title":"Genome-wide analysis of the JAZ subfamily of transcription factors and functional verification of BnC08.JAZ1-1 in Brassica napus.","date":"2022","source":"Biotechnology for biofuels and bioproducts","url":"https://pubmed.ncbi.nlm.nih.gov/36096884","citation_count":9,"is_preprint":false},{"pmid":"36922795","id":"PMC_36922795","title":"Genome-wide identification of the TIFY family reveals JAZ subfamily function in response to hormone treatment in Betula platyphylla.","date":"2023","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/36922795","citation_count":9,"is_preprint":false},{"pmid":"33987474","id":"PMC_33987474","title":"MiR-542-3p Suppresses Neuroblastoma Cell Proliferation and Invasion by Downregulation of KDM1A and ZNF346.","date":"2020","source":"Open life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33987474","citation_count":8,"is_preprint":false},{"pmid":"39043058","id":"PMC_39043058","title":"Genome-wide identification and characterization of the JAZ gene family in Gynostemma pentaphyllum reveals the COI1/JAZ/MYC2 complex potential involved in the regulation of the MeJA-induced gypenoside biosynthesis.","date":"2024","source":"Plant physiology and biochemistry : PPB","url":"https://pubmed.ncbi.nlm.nih.gov/39043058","citation_count":8,"is_preprint":false},{"pmid":"38994074","id":"PMC_38994074","title":"Evaluation of resistance patterns and bioremoval efficiency of hydrocarbons and heavy metals by the mycobiome of petroleum refining wastewater in Jazan with assessment of molecular typing and cytotoxicity of Scedosporium apiospermum JAZ-20.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38994074","citation_count":7,"is_preprint":false},{"pmid":"21715977","id":"PMC_21715977","title":"JAZ mediates G1 cell cycle arrest by interacting with and inhibiting E2F1.","date":"2011","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21715977","citation_count":6,"is_preprint":false},{"pmid":"38188528","id":"PMC_38188528","title":"Two distinct modes of action of molecular glues in the plant hormone co-receptor COI1-JAZ system.","date":"2023","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/38188528","citation_count":5,"is_preprint":false},{"pmid":"23615997","id":"PMC_23615997","title":"Modified bimolecular fluorescence complementation assay to study the inhibition of transcription complex formation by JAZ proteins.","date":"2013","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/23615997","citation_count":5,"is_preprint":false},{"pmid":"38926665","id":"PMC_38926665","title":"Genome-wide identification of JAZ gene family members in autotetraploid cultivated alfalfa (Medicago sativa subsp. sativa) and expression analysis under salt stress.","date":"2024","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/38926665","citation_count":4,"is_preprint":false},{"pmid":"40654046","id":"PMC_40654046","title":"Pepper JAZ Protein CaJAZ1-06 Negatively Regulates Drought Stress and Abscisic Acid Signaling.","date":"2025","source":"Physiologia plantarum","url":"https://pubmed.ncbi.nlm.nih.gov/40654046","citation_count":4,"is_preprint":false},{"pmid":"37373020","id":"PMC_37373020","title":"Revealing the Roles of the JAZ Family in Defense Signaling and the Agarwood Formation Process in Aquilaria sinensis.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37373020","citation_count":4,"is_preprint":false},{"pmid":"37741055","id":"PMC_37741055","title":"Comprehensive analysis of JAZ family members in Ginkgo biloba reveals the regulatory role of the GbCOI1/GbJAZs/GbMYC2 module in ginkgolide biosynthesis.","date":"2024","source":"Tree physiology","url":"https://pubmed.ncbi.nlm.nih.gov/37741055","citation_count":4,"is_preprint":false},{"pmid":"38891302","id":"PMC_38891302","title":"Jasmonate ZIM Domain Protein (JAZ) Gene SLJAZ15 Increases Resistance to Orobanche aegyptiaca in Tomato.","date":"2024","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/38891302","citation_count":3,"is_preprint":false},{"pmid":"40076978","id":"PMC_40076978","title":"Genome-Wide Analysis of the JAZ Gene Family in Potato and Functional Verification of StJAZ23 Under Drought Stress.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40076978","citation_count":3,"is_preprint":false},{"pmid":"34720056","id":"PMC_34720056","title":"Differential regulation of jasmonate responses in multiple jaz mutants.","date":"2021","source":"Plant signaling & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/34720056","citation_count":3,"is_preprint":false},{"pmid":"39566784","id":"PMC_39566784","title":"Genome-wide identification of the eggplant jasmonate ZIM-domain (JAZ) gene family and functional characterization of SmJAZ10 in modulating chlorophyll synthesis in leaves.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39566784","citation_count":3,"is_preprint":false},{"pmid":"40045540","id":"PMC_40045540","title":"The Nuclear Effector MiISE23 From Meloidogyne incognita Targets JAZ Proteins and Suppresses Jasmonate Signalling, Increasing Host Susceptibility.","date":"2025","source":"Plant, cell & environment","url":"https://pubmed.ncbi.nlm.nih.gov/40045540","citation_count":3,"is_preprint":false},{"pmid":"36361657","id":"PMC_36361657","title":"Genome-Wide Identification and Variation Analysis of JAZ Family Reveals BnaJAZ8.C03 Involved in the Resistance to Plasmodiophora brassicae in Brassica napus.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36361657","citation_count":3,"is_preprint":false},{"pmid":"39607638","id":"PMC_39607638","title":"Genome-wide survey and expression analysis of JAZ genes in watermelon (Citrullus lanatus).","date":"2024","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/39607638","citation_count":2,"is_preprint":false},{"pmid":"40763068","id":"PMC_40763068","title":"Genome-Wide Identification and Analysis of the JAZ Gene Family in Rapeseed Reveal JAZ2 and JAZ3 Roles in Drought and Salt Stress Tolerance.","date":"2025","source":"Journal of agricultural and food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40763068","citation_count":2,"is_preprint":false},{"pmid":"40183817","id":"PMC_40183817","title":"Genome-wide insights into the nomenclature, evolution and expression of tobacco TIFY/JAZ genes.","date":"2025","source":"Planta","url":"https://pubmed.ncbi.nlm.nih.gov/40183817","citation_count":2,"is_preprint":false},{"pmid":"40429827","id":"PMC_40429827","title":"Genome-Wide Analysis and Expression Profiling of the JAZ Gene Family in Response to Abiotic Stress in Alfalfa.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40429827","citation_count":2,"is_preprint":false},{"pmid":"40669160","id":"PMC_40669160","title":"Characterization of the JAZ family in Osmanthus fragrans and the role of OfLJAZ2 in flavonoid synthesis mediated regulation of salt and drought stress tolerance.","date":"2025","source":"Plant physiology and biochemistry : PPB","url":"https://pubmed.ncbi.nlm.nih.gov/40669160","citation_count":2,"is_preprint":false},{"pmid":"40158571","id":"PMC_40158571","title":"Temporal transcriptome and genome-wide identification of lily jasmonate ZIM-domain (JAZ) protein gene family reveals the roles of LfJAZ3 and LfJAZ12 in bulb development in Lilium fargesii.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40158571","citation_count":2,"is_preprint":false},{"pmid":"40863553","id":"PMC_40863553","title":"JA Signaling Inhibitor JAZ Is Involved in Regulation of AM Symbiosis with Cassava, Including Symbiosis Establishment and Cassava Growth.","date":"2025","source":"Journal of fungi (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/40863553","citation_count":2,"is_preprint":false},{"pmid":"39996821","id":"PMC_39996821","title":"Genome-Wide Identification and Analysis of the JAZ Gene Family in Artemisia argyi.","date":"2025","source":"Current issues in molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/39996821","citation_count":1,"is_preprint":false},{"pmid":"39989054","id":"PMC_39989054","title":"[Regulatory roles of JAZ in the growth and development of horticultural plants].","date":"2025","source":"Sheng wu gong cheng xue bao = Chinese journal of biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/39989054","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49201,"output_tokens":2511,"usd":0.092634,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9457,"output_tokens":2573,"usd":0.055805,"stage2_stop_reason":"end_turn"},"total_usd":0.148439,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify which papers are about the human/mammalian ZNF346 protein (also known as JAZ in mammals - a C2H2 zinc finger dsRNA-binding protein) versus plant JAZ/JAZMONATE ZIM-DOMAIN proteins (a completely different protein family that happens to share the \"JAZ\" alias).\n\nThe human ZNF346/JAZ protein is characterized by: C2H2-type zinc fingers, dsRNA binding, nuclear/nucleolar localization, roles in apoptosis/cell cycle, and interaction with p53 and E2F1. Papers [26], [30], [55], [57], [79] describe this mammalian protein. Papers [43] and [76] describe ZNF346 in neuroblastoma context.\n\nAll other papers (plant JAZ/JAZMONATE ZIM-DOMAIN proteins) are symbol collisions - completely different protein family, different organisms, different function.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"ZNF346 (JAZ) contains four C2H2-type zinc finger motifs connected by long linker sequences and preferentially binds double-stranded RNA (dsRNA) or RNA/DNA hybrids rather than DNA. The zinc finger domains are required both for dsRNA binding and for nucleolar localization. Forced expression of ZNF346 potently induces apoptosis in murine fibroblast cells.\",\n      \"method\": \"Cloning and characterization; mutagenesis of individual zinc finger motifs; subcellular localization; overexpression apoptosis assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct mutagenesis linking zinc finger domains to both dsRNA binding and nuclear localization, with functional apoptosis readout; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"10488071\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"ZNF346 (JAZ) is a cargo protein for exportin-5 and undergoes nucleocytoplasmic shuttling. JAZ binds exportin-5 in a Ran-GTP- and dsRNA-dependent manner; exportin-5 stimulates JAZ nuclear export, and gene silencing of exportin-5 reduces shuttling. JAZ also binds ILF3 in an RNA-independent manner requiring the dsRNA-binding domains of ILF3, and JAZ, ILF3, and exportin-5 can form a heteromeric complex with Ran-GTP and dsRNA. Nuclear import of JAZ does not require energy or cytosol but is blocked by low temperature, suggesting facilitated diffusion.\",\n      \"method\": \"Co-immunoprecipitation; permeabilized cell nuclear export assay; siRNA knockdown of exportin-5; Ran-GTP binding assay; nucleocytoplasmic shuttling assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal binding assays, siRNA knockdown, permeabilized cell reconstitution, and multiple orthogonal methods establishing the export mechanism\",\n      \"pmids\": [\"15254228\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"ZNF346 (JAZ) physically associates with p53 and stimulates p53 transcriptional activity, mediating G1 cell-cycle arrest and apoptosis in a p53-dependent mechanism involving upregulation of p21 and BAX, dephosphorylation of Rb, and repression of cyclin A. The interaction requires p53's C-terminal regulatory domain but is independent of dsRNA. The dsRNA-binding zinc finger domains are required for nuclear localization and for stimulatory activity in vivo. siRNA knockdown of endogenous ZNF346 inhibits p53 transcriptional activity, decreases the G1/G0 population, and attenuates stress-induced cell death.\",\n      \"method\": \"Co-immunoprecipitation; in vitro binding assay; reporter assays; siRNA knockdown; flow cytometry cell cycle analysis; p53-null cell complementation\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vitro direct binding plus siRNA loss-of-function with specific cell cycle/apoptosis phenotypes, p53-null complementation, multiple orthogonal methods in single study\",\n      \"pmids\": [\"16931621\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ZNF346 (JAZ) directly interacts with E2F1, associating with E2F1's central DNA binding/dimerization region and its C-terminal transactivation domain. ZNF346 represses E2F1 transcriptional activity, inhibits E2F1's specific DNA binding activity, represses cyclin A expression, and inhibits G1/S transition. This mechanism is independent of p53. siRNA knockdown of endogenous ZNF346 increases E2F transcriptional activity and releases cells from G1 arrest.\",\n      \"method\": \"Co-immunoprecipitation; in vitro direct binding assay; reporter assays; siRNA knockdown; cell cycle analysis\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vitro direct binding, siRNA loss-of-function with specific transcriptional and cell cycle phenotypes, domain mapping, multiple orthogonal methods\",\n      \"pmids\": [\"21715977\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ZNF346 (JAZ) preferentially binds dsRNA with no detectable sequence specificity; affinity is unaffected by local structural features (loops, overhangs, bulges) provided sufficient A-form RNA (~18 bp per zinc finger) is present. Full-length JAZ with all four C2H2 zinc fingers (ZF1-4) has the highest dsRNA affinity; two-finger constructs ZF12 and ZF23 have lower affinity; ZF34 binds more weakly; ZF4 alone has no measurable RNA-binding affinity. Quantitative NMR and ITC data fitted to a two-site binding model yielded Kd1 ~10 μM and Kd2 ~100 μM. HADDOCK-generated models indicate single zinc fingers bind the RNA backbone without sequence specificity via contacts between the RNA minor groove and N-terminal β strands and the major groove and helix-kink-helix motif residues.\",\n      \"method\": \"Electrophoretic mobility shift assays (EMSA); isothermal titration calorimetry (ITC); nuclear magnetic resonance (NMR) spectroscopy; HADDOCK computational docking\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — quantitative in vitro binding (ITC + NMR + EMSA) with domain-deletion series and structural modeling; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"24521053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"miR-1247 directly targets the 3′UTR of ZNF346 mRNA in neuroblastoma cells, repressing ZNF346 protein expression. siRNA-mediated knockdown of ZNF346 suppresses neuroblastoma cell proliferation, induces G0/G1 cell cycle arrest, and promotes apoptosis, phenocopying miR-1247 overexpression.\",\n      \"method\": \"Luciferase reporter assay (3′UTR targeting); siRNA knockdown; MTT assay; colony formation assay; flow cytometry; Western blotting\",\n      \"journal\": \"Biological research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct 3′UTR luciferase validation of miR-1247 targeting ZNF346, siRNA knockdown phenocopying miR-1247 overexpression; single lab with two orthogonal methods\",\n      \"pmids\": [\"29793538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"miR-542-3p reduces ZNF346 protein levels in neuroblastoma cells through direct interaction, and ZNF346 upregulation weakens the anti-proliferative and anti-invasive effects of miR-542-3p, indicating that ZNF346 is a functional downstream target mediating miR-542-3p's tumor-suppressive activity.\",\n      \"method\": \"miR-542-3p overexpression; Western blotting for ZNF346; ZNF346 rescue overexpression; cell proliferation and invasion assays; in vivo tumor growth assay\",\n      \"journal\": \"Open life sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, no direct 3′UTR luciferase validation for ZNF346 reported; rescue experiment supports functional link but limited mechanistic detail\",\n      \"pmids\": [\"33987474\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNF346 (JAZ) is a nucleolar C2H2-type zinc finger protein that preferentially binds double-stranded RNA in a sequence-nonspecific manner through its first three zinc fingers; it shuttles between nucleus and cytoplasm via exportin-5 in a Ran-GTP/dsRNA-dependent export mechanism with facilitated diffusion re-entry, forms a complex with ILF3, acts as a positive regulator of p53 transcriptional activity by directly binding p53's C-terminal domain to mediate G1 arrest and apoptosis, and independently represses cell proliferation by directly binding and inhibiting E2F1 transcriptional and DNA-binding activity, thereby providing dual p53-dependent and p53-independent mechanisms of cell-cycle control.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNF346 (JAZ) is a nucleolar C2H2-type zinc finger protein that functions as a double-stranded RNA-binding regulator of cell-cycle progression and apoptosis [#0, #2]. Its four zinc fingers, connected by long linkers, preferentially bind A-form dsRNA or RNA/DNA hybrids in a sequence-nonspecific manner, with the full-length four-finger array providing maximal affinity and the same zinc finger domains being required for nucleolar localization [#0, #4]. ZNF346 is an exportin-5 cargo that shuttles between nucleus and cytoplasm in a Ran-GTP- and dsRNA-dependent manner, re-entering the nucleus by facilitated diffusion, and it assembles with ILF3 and exportin-5 into a heteromeric Ran-GTP/dsRNA complex [#1]. Functionally, ZNF346 exerts dual control over the G1/S transition: it physically associates with the C-terminal regulatory domain of p53 to stimulate p53 transcriptional activity, driving p21 and BAX upregulation, Rb dephosphorylation, cyclin A repression, G1 arrest, and apoptosis [#2], and in a p53-independent arm it directly binds E2F1, inhibiting E2F1 DNA binding and transactivation to repress cyclin A and block G1/S progression [#3]. Consistent with this anti-proliferative role, ZNF346 is a target of tumor-suppressive microRNAs in neuroblastoma, where its loss suppresses proliferation and promotes apoptosis [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established that ZNF346 is a zinc finger protein with an unexpected nucleic-acid preference, defining it as a dsRNA-binding rather than DNA-binding protein and linking it to apoptosis.\",\n      \"evidence\": \"Cloning, zinc finger mutagenesis, subcellular localization, and overexpression apoptosis assay in murine fibroblasts\",\n      \"pmids\": [\"10488071\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not identify physiological dsRNA targets or binding partners\", \"Mechanism linking dsRNA binding to apoptosis not resolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Resolved how ZNF346 moves between compartments, defining it as an exportin-5 cargo and identifying ILF3 as a stable partner in a Ran-GTP/dsRNA complex.\",\n      \"evidence\": \"Co-immunoprecipitation, permeabilized-cell nuclear export assay, exportin-5 siRNA knockdown, and Ran-GTP binding assay\",\n      \"pmids\": [\"15254228\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of nucleocytoplasmic shuttling for downstream signaling not established\", \"Cargo carried by ZNF346 during export not identified\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined the first regulatory output of ZNF346, showing it is a positive cofactor for p53 that drives p53-dependent G1 arrest and apoptosis.\",\n      \"evidence\": \"Co-IP, in vitro binding, reporter assays, siRNA knockdown, flow cytometry, and p53-null complementation\",\n      \"pmids\": [\"16931621\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the p53 C-terminal interaction not determined\", \"Whether dsRNA binding modulates p53 cofactor activity not resolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed ZNF346 acts through a second, p53-independent route by directly binding and inhibiting E2F1, establishing dual mechanisms of cell-cycle control.\",\n      \"evidence\": \"Co-IP, in vitro direct binding, domain mapping, reporter assays, siRNA knockdown, and cell cycle analysis\",\n      \"pmids\": [\"21715977\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contribution of p53 vs E2F1 arms in vivo not quantified\", \"How the two activities are coordinated unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Provided the quantitative and structural basis for dsRNA recognition, defining affinity contributions of individual zinc fingers and the sequence-nonspecific A-form recognition mode.\",\n      \"evidence\": \"EMSA, ITC, NMR, and HADDOCK docking with domain-deletion constructs\",\n      \"pmids\": [\"24521053\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No experimental high-resolution complex structure\", \"Physiological dsRNA ligands and how RNA binding integrates with transcriptional regulation not addressed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placed ZNF346 in a tumor context as a proliferation-promoting target of regulatory microRNAs, contrasting with its anti-proliferative biochemical activities.\",\n      \"evidence\": \"miR-1247 3'UTR luciferase validation and siRNA knockdown (2018); miR-542-3p overexpression with ZNF346 rescue and in vivo tumor assays (2020)\",\n      \"pmids\": [\"29793538\", \"33987474\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"miR-542-3p targeting of ZNF346 lacks direct 3'UTR luciferase validation\", \"How a p53/E2F1 cell-cycle regulator promotes neuroblastoma proliferation mechanistically unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ZNF346's dsRNA binding, exportin-5 shuttling, and ILF3 association mechanistically connect to its p53/E2F1 transcriptional functions remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No identified endogenous dsRNA ligand linking RNA binding to transcriptional regulation\", \"Physiological role of the ILF3/exportin-5 complex not defined\", \"No structural model of the p53 or E2F1 complexes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ILF3\", \"XPO5\", \"TP53\", \"E2F1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}