{"gene":"DDX42","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":2002,"finding":"DDX42 (SF3b125) was identified as a novel protein associated with the human 17S U2 snRNP and its stable subunit SF3b by mass spectrometry. SF3b125 dissociates at the time of 17S U2 snRNP formation, suggesting it may facilitate assembly of the 17S U2 snRNP. Immunofluorescence/FISH studies revealed SF3b125 is enriched in Cajal bodies, in contrast to SF3b155 and SF3a120, indicating a differential subnuclear distribution linked to U2 snRNP assembly.","method":"Mass spectrometry, immunodepletion, immunofluorescence/FISH","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — mass spectrometry identification plus immunodepletion and localization experiments, replicated in the context of spliceosome assembly characterization","pmids":["12234937"],"is_preprint":false},{"year":2006,"finding":"Recombinant Ddx42p is an RNA-binding protein and NTPase with preference for ATP; its ATP hydrolysis is enhanced by RNA substrates. It acts as a non-processive RNA helicase, and RNA unwinding is promoted by a single-strand binding protein (T4gp32). In the ADP-bound state, Ddx42p mediates efficient annealing of complementary RNA strands and displaces the ss binding protein. Thus the adenosine nucleotide cofactor (ATP vs ADP) acts as a molecular switch controlling strand separation versus strand annealing activities.","method":"In vitro biochemical assays: NTPase assay, RNA helicase/unwinding assay, RNA annealing assay with recombinant protein","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple orthogonal in vitro enzymatic assays (NTPase, helicase, annealing) with recombinant protein in a single rigorous study","pmids":["16397294"],"is_preprint":false},{"year":2008,"finding":"The N-terminus of DDX42 was identified as specifically binding to JEV NS4A protein in vitro via co-immunoprecipitation, identified using a phage display human brain cDNA library. DDX42 and JEV NS4A showed partial co-localization in human medulloblastoma TE-671 cells by confocal microscopy. Expression of N-terminal DDX42 was able to overcome JEV NS4A-induced antagonism of IFN responses.","method":"Phage display, co-immunoprecipitation, confocal microscopy, IFN reporter assay","journal":"Virus research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP and colocalization with functional rescue experiment, single lab, multiple complementary methods","pmids":["18588927"],"is_preprint":false},{"year":2019,"finding":"DDX42 was identified as a G-quadruplex (G4)-binding protein in an unbiased genome-wide shRNA screen in human cells treated with G4-stabilizing small molecules; DDX42 silencing in combination with G4 ligand treatment enhanced cell killing.","method":"Genome-wide shRNA screen, G4 ligand treatment","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genome-wide screen identified DDX42 as G4-binding, single lab, limited mechanistic follow-up on DDX42 specifically","pmids":["31287417"],"is_preprint":false},{"year":2019,"finding":"DDX42 interacts with paxillin (a focal adhesion adaptor protein) as demonstrated by reciprocal co-precipitation (His-tagged paxillin pull-down followed by anti-DDX42 western blot, and His-tagged DDX42 pull-down followed by anti-paxillin western blot). DDX42 preferentially interacts with paxillin S273A mutant over S273D mutant. DDX42 overexpression delayed IL-3 deprivation-induced apoptosis and promoted restoration of elongated cell shape in Ba/F3 cells.","method":"Ni-NTA pull-down, LC-MS, western blotting, cell morphology and apoptosis assays","journal":"Animal cells and systems","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — reciprocal pull-down with functional overexpression phenotype, single lab, two complementary methods","pmids":["30834153"],"is_preprint":false},{"year":2022,"finding":"Cancer-associated SF3B1 mutation K700E reduces interaction of DDX42 and DDX46 with SF3B1. Overexpression of DDX42 restored its decreased interaction with K700E-mutated SF3B1 and suppressed some alternative RNA splicing associated with the SF3B1 mutation. A DDX42 mutation that decreased ATP hydrolysis activity abolished the suppressive effect on alternative splicing, demonstrating that the ATP hydrolysis activity of DDX42 is required for its role in regulating RNA splicing downstream of SF3B1.","method":"Co-immunoprecipitation, overexpression, ATPase-dead mutant, splicing assays","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP, ATPase-dead mutagenesis, and splicing rescue assays, single lab","pmids":["35652295"],"is_preprint":false},{"year":2022,"finding":"DDX42 is an intrinsic antiviral inhibitor of HIV-1 and other positive-strand RNA viruses (CHIKV, SARS-CoV-2) and LINE-1 retrotransposition, but does not impact replication of several negative-strand RNA viruses. Depletion of endogenous DDX42 increases HIV-1 DNA accumulation and infection; overexpression inhibits infection; a dominant-negative mutant increases infection. Proximity ligation assays show DDX42 near viral elements; cross-linking RNA immunoprecipitation confirms specific interaction of DDX42 with RNAs from sensitive viruses. Recombinant DDX42 inhibits HIV-1 reverse transcription in vitro, suggesting a direct mode of action on viral ribonucleoprotein complexes.","method":"CRISPR screen, KD/KO, overexpression, dominant-negative mutant, proximity ligation assay, cross-linking RNA immunoprecipitation, in vitro reverse transcription assay, RNA-seq","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal methods including in vitro reconstitution, CLIP, proximity ligation, genetic perturbation, and dominant-negative mutagenesis in a single rigorous study","pmids":["36161446"],"is_preprint":false},{"year":2023,"finding":"Cryo-EM structures of the DDX42-SF3b complex and a DDX42-U2 snRNP assembly precursor reveal that DDX42 is anchored on SF3B1 through its N-terminal sequences, with its N-plug occupying the RNA path of SF3B1, in a binding mode strikingly analogous to DDX46. In the DDX42-U2 complex, the N-terminus remains anchored on SF3B1 but the helicase domain is displaced by U2 snRNA and TAT-SF1. In vitro assays show DDX42 and DDX46 are mutually exclusive in binding to SF3b. Cancer-driving SF3B1 mutations target residues in the RNA path that directly interact with DDX42 and DDX46.","method":"Cryo-EM structure determination, in vitro binding assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structures plus in vitro binding assays, multiple orthogonal methods establishing mechanism of U2 snRNP assembly","pmids":["36797247"],"is_preprint":false},{"year":2024,"finding":"Single-molecule imaging of U2AF in vitro and in vivo established a kinetic model of splice site selection in which DDX42 helicase activity increases selectivity to the underlying U2AF binding site during spliceosome assembly, while still allowing efficient forward progression. DDX42 thus catalyzes a 'partial kinetic proofreading' mechanism for 3' splice site selection while U2AF is in complex with the spliceosome.","method":"Single-molecule fluorescence imaging in vitro and in vivo, kinetic modeling, alternative splicing analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single-molecule in vitro and in vivo imaging with mechanistic kinetic modeling, single preprint lab study","pmids":["39372787"],"is_preprint":true},{"year":2025,"finding":"DDX42 promotes GRB2 mRNA maturation in hepatocellular carcinoma cells, contributing to activation of the PI3K/AKT pathway, cell proliferation, and resistance to radiation and sorafenib. Knockdown of DDX42 inhibited HCC cell growth, increased radiosensitivity, enhanced sorafenib efficacy, and inactivated the PI3K/AKT pathway in vitro and in a xenograft model.","method":"Knockdown/overexpression, mRNA maturation assay, PI3K/AKT pathway readouts, subcutaneous xenograft mouse model","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss- and gain-of-function with defined pathway readout and in vivo model, single lab study","pmids":["40831000"],"is_preprint":false}],"current_model":"DDX42 is a nuclear DEAD-box RNA helicase that functions as a component of the SF3b/17S U2 snRNP spliceosomal complex, where its N-terminus anchors to SF3B1 and its ATP hydrolysis activity regulates RNA splice site selection and suppresses aberrant splicing associated with oncogenic SF3B1 mutations; biochemically, DDX42 uses ATP vs. ADP binding as a switch between RNA strand unwinding and RNA annealing activities; beyond splicing, DDX42 acts as an intrinsic antiviral restriction factor that directly binds and inhibits positive-strand RNA viruses and retroviruses (including HIV-1, CHIKV, and SARS-CoV-2) by interacting with viral RNA and inhibiting reverse transcription, and also promotes GRB2 mRNA maturation to activate PI3K/AKT signaling in cancer cells."},"narrative":{"mechanistic_narrative":"DDX42 is a DEAD-box RNA helicase that functions in spliceosome assembly as a component of the SF3b/17S U2 snRNP machinery and that doubles as an intrinsic antiviral restriction factor [PMID:12234937, PMID:36161446]. It was first identified as SF3b125, a protein associated with the human 17S U2 snRNP and its stable SF3b core that dissociates upon mature 17S U2 snRNP formation and is enriched in Cajal bodies, marking it as an assembly factor [PMID:12234937]. Cryo-EM structures show DDX42 anchored on SF3B1 through its N-terminal sequences, with its N-plug occupying the SF3B1 RNA path in a binding mode analogous to and mutually exclusive with DDX46; upon U2 snRNP assembly the N-terminus remains anchored while the helicase domain is displaced by U2 snRNA and TAT-SF1 [PMID:36797247]. As an enzyme, DDX42 is an RNA-stimulated NTPase that uses ATP versus ADP binding as a molecular switch between non-processive RNA strand unwinding and RNA annealing [PMID:16397294], and its ATP hydrolysis activity is required to suppress aberrant alternative splicing caused by oncogenic SF3B1-K700E, which weakens the DDX42-SF3B1 interaction [PMID:35652295]. Independently of splicing, DDX42 directly binds the RNA of positive-strand RNA viruses and retroviruses (HIV-1, CHIKV, SARS-CoV-2) and LINE-1 elements and inhibits HIV-1 reverse transcription in vitro, acting on viral ribonucleoprotein complexes [PMID:36161446]. In cancer cells DDX42 promotes GRB2 mRNA maturation to activate PI3K/AKT signaling and drive proliferation and therapy resistance [PMID:40831000].","teleology":[{"year":2002,"claim":"Establishing that DDX42 (SF3b125) is a U2 snRNP-associated factor placed it within the spliceosome assembly pathway rather than the mature snRNP.","evidence":"Mass spectrometry, immunodepletion, and immunofluorescence/FISH on human 17S U2 snRNP/SF3b","pmids":["12234937"],"confidence":"High","gaps":["Did not define the molecular contacts anchoring DDX42 to SF3b","Functional role in assembly inferred from dissociation timing, not directly tested"]},{"year":2006,"claim":"Biochemical reconstitution defined DDX42 as an RNA-stimulated NTPase whose nucleotide state switches it between unwinding and annealing, giving the protein a defined enzymatic logic.","evidence":"In vitro NTPase, helicase, and RNA annealing assays with recombinant protein","pmids":["16397294"],"confidence":"High","gaps":["Physiological RNA substrates not identified","Link between in vitro switch and spliceosome function not established"]},{"year":2008,"claim":"Identification of an interaction with JEV NS4A and rescue of IFN antagonism hinted at an antiviral/immune-modulatory role beyond splicing.","evidence":"Phage display, co-immunoprecipitation, confocal colocalization, IFN reporter assay in TE-671 cells","pmids":["18588927"],"confidence":"Medium","gaps":["Single lab, in vitro co-IP without endogenous validation","Mechanism connecting DDX42 N-terminus to IFN response unresolved"]},{"year":2019,"claim":"Unbiased screens linked DDX42 to G-quadruplex RNA/DNA biology and to a focal adhesion adaptor, broadening its candidate interaction landscape.","evidence":"Genome-wide shRNA screen with G4 ligands; reciprocal Ni-NTA pull-down with paxillin plus morphology/apoptosis assays","pmids":["31287417","30834153"],"confidence":"Medium","gaps":["G4 binding by DDX42 not directly demonstrated biochemically","Paxillin interaction lacks mechanistic context or endogenous confirmation"]},{"year":2022,"claim":"Linking ATP-hydrolysis-dependent DDX42 activity to suppression of SF3B1-mutant aberrant splicing connected its enzymatic switch to oncogenic spliceosome dysfunction.","evidence":"Co-IP, overexpression rescue, ATPase-dead mutant, and splicing assays in cells with SF3B1-K700E","pmids":["35652295"],"confidence":"Medium","gaps":["Direct RNA targets of the splicing-suppressive activity not mapped","Single lab, no structural basis at this stage"]},{"year":2022,"claim":"Demonstrating direct viral RNA binding and inhibition of reverse transcription established DDX42 as a genuine intrinsic antiviral restriction factor with selectivity for positive-strand RNA viruses and retroelements.","evidence":"CRISPR screen, KD/KO, overexpression, dominant-negative mutant, PLA, CLIP, in vitro reverse transcription assay, RNA-seq","pmids":["36161446"],"confidence":"High","gaps":["Whether antiviral and splicing roles use the same domains/activity unresolved","Basis for virus selectivity not fully defined"]},{"year":2023,"claim":"Cryo-EM structures revealed how DDX42 docks onto SF3B1 via its N-plug and how cancer mutations and DDX46 competition map to the same RNA path, providing the structural mechanism of U2 snRNP assembly.","evidence":"Cryo-EM of DDX42-SF3b and DDX42-U2 snRNP precursor plus in vitro binding assays","pmids":["36797247"],"confidence":"High","gaps":["Functional consequence of DDX42/DDX46 exchange during assembly not kinetically resolved","Helicase domain displacement role in catalysis not directly tested"]},{"year":2024,"claim":"Single-molecule kinetics framed DDX42 helicase activity as a partial kinetic proofreading mechanism that tunes 3' splice site selectivity at U2AF.","evidence":"Single-molecule fluorescence imaging of U2AF in vitro and in vivo with kinetic modeling (preprint)","pmids":["39372787"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Quantitative model awaits independent confirmation"]},{"year":2025,"claim":"Showing DDX42 promotes GRB2 mRNA maturation to drive PI3K/AKT signaling tied its RNA-processing activity to cancer proliferation and therapy resistance.","evidence":"Knockdown/overexpression, mRNA maturation assay, PI3K/AKT readouts, and xenograft model in HCC cells","pmids":["40831000"],"confidence":"Medium","gaps":["Direct binding of DDX42 to GRB2 transcript not structurally defined","Single lab; generality across cancer types untested"]},{"year":null,"claim":"How DDX42's helicase enzymology is partitioned and coordinated across its splicing, antiviral, and oncogenic mRNA-maturation roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model relating ATP-switch activity to substrate choice across contexts","Whether nuclear splicing and cytoplasmic/viral functions reflect distinct pools is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1,6]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[1,5]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[1]},{"term_id":"GO:0016787","term_label":"hydrolase activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,7]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[6]}],"complexes":["SF3b","17S U2 snRNP"],"partners":["SF3B1","DDX46","TAT-SF1","U2AF","PXN","JEV NS4A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86XP3","full_name":"ATP-dependent RNA helicase DDX42","aliases":["DEAD box protein 42","RNA helicase-like protein","RHELP","RNA helicase-related protein","RNAHP","SF3b DEAD box protein","Splicing factor 3B-associated 125 kDa protein","SF3b125"],"length_aa":938,"mass_kda":103.0,"function":"ATP-dependent RNA helicase that binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures (PubMed:16397294). Unwinding is promoted in the presence of single-strand binding proteins (PubMed:16397294). Also mediates RNA duplex formation thereby displacing the single-strand RNA binding protein (PubMed:16397294). ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands (PubMed:16397294). Required for assembly of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs: DDX42 associates transiently with the SF3B subcomplex of the 17S U2 SnRNP complex and is released after fulfilling its role in the assembly of 17S U2 SnRNP (PubMed:12234937, PubMed:36797247). Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2 (PubMed:19377511). Relocalizes TP53BP2 to the cytoplasm (PubMed:19377511)","subcellular_location":"Nucleus, Cajal body; Nucleus speckle","url":"https://www.uniprot.org/uniprotkb/Q86XP3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DDX42","classification":"Common Essential","n_dependent_lines":1189,"n_total_lines":1208,"dependency_fraction":0.984271523178808},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SF3B6","stoichiometry":10.0},{"gene":"SF3A1","stoichiometry":4.0},{"gene":"SF3A2","stoichiometry":4.0},{"gene":"SF3A3","stoichiometry":4.0},{"gene":"SF3B1","stoichiometry":4.0},{"gene":"SRP9","stoichiometry":4.0},{"gene":"CD2BP2","stoichiometry":0.2},{"gene":"CPSF6","stoichiometry":0.2},{"gene":"DNAJC8","stoichiometry":0.2},{"gene":"RBM17","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DDX42","total_profiled":1310},"omim":[{"mim_id":"617848","title":"DEAD-BOX HELICASE 46; DDX46","url":"https://www.omim.org/entry/617848"},{"mim_id":"613369","title":"DEAD-BOX HELICASE 42; DDX42","url":"https://www.omim.org/entry/613369"},{"mim_id":"602143","title":"TUMOR PROTEIN p53-BINDING PROTEIN 2; TP53BP2","url":"https://www.omim.org/entry/602143"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nuclear speckles","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DDX42"},"hgnc":{"alias_symbol":["RNAHP","RHELP","SF3b125","SF3B8"],"prev_symbol":[]},"alphafold":{"accession":"Q86XP3","domains":[{"cath_id":"3.40.50.300","chopping":"223-462","consensus_level":"high","plddt":92.7445,"start":223,"end":462},{"cath_id":"3.40.50.300","chopping":"472-641","consensus_level":"high","plddt":88.1304,"start":472,"end":641}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86XP3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86XP3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86XP3-F1-predicted_aligned_error_v6.png","plddt_mean":66.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DDX42","jax_strain_url":"https://www.jax.org/strain/search?query=DDX42"},"sequence":{"accession":"Q86XP3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86XP3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86XP3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86XP3"}},"corpus_meta":[{"pmid":"12234937","id":"PMC_12234937","title":"Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein.","date":"2002","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/12234937","citation_count":237,"is_preprint":false},{"pmid":"31287417","id":"PMC_31287417","title":"Genetic interactions of G-quadruplexes in humans.","date":"2019","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/31287417","citation_count":100,"is_preprint":false},{"pmid":"23678170","id":"PMC_23678170","title":"Epstein-Barr virus-encoded microRNA BART15-3p promotes cell apoptosis partially by targeting BRUCE.","date":"2013","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/23678170","citation_count":97,"is_preprint":false},{"pmid":"36006669","id":"PMC_36006669","title":"DExH/D-box helicases at the frontline of intrinsic and innate immunity against viral infections.","date":"2022","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/36006669","citation_count":49,"is_preprint":false},{"pmid":"16397294","id":"PMC_16397294","title":"Ddx42p--a human DEAD box protein with RNA chaperone activities.","date":"2006","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/16397294","citation_count":49,"is_preprint":false},{"pmid":"36797247","id":"PMC_36797247","title":"Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/36797247","citation_count":48,"is_preprint":false},{"pmid":"18588927","id":"PMC_18588927","title":"Interferon antagonist function of Japanese encephalitis virus NS4A and its interaction with DEAD-box RNA helicase DDX42.","date":"2008","source":"Virus research","url":"https://pubmed.ncbi.nlm.nih.gov/18588927","citation_count":48,"is_preprint":false},{"pmid":"24094746","id":"PMC_24094746","title":"Formation of chimeric genes by copy-number variation as a mutational mechanism in schizophrenia.","date":"2013","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24094746","citation_count":36,"is_preprint":false},{"pmid":"35072517","id":"PMC_35072517","title":"Temporal Modulation of Differential Alternative Splicing in HaCaT Human Keratinocyte Cell Line Chronically Exposed to Arsenic for up to 28 Wk.","date":"2022","source":"Environmental health perspectives","url":"https://pubmed.ncbi.nlm.nih.gov/35072517","citation_count":23,"is_preprint":false},{"pmid":"37306722","id":"PMC_37306722","title":"ZNF384-Related Fusion Genes in Acute Lymphoblastic Leukemia.","date":"2023","source":"Cancer control : journal of the Moffitt Cancer Center","url":"https://pubmed.ncbi.nlm.nih.gov/37306722","citation_count":19,"is_preprint":false},{"pmid":"35652295","id":"PMC_35652295","title":"Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42.","date":"2022","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35652295","citation_count":16,"is_preprint":false},{"pmid":"36161446","id":"PMC_36161446","title":"The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses.","date":"2022","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/36161446","citation_count":15,"is_preprint":false},{"pmid":"40537811","id":"PMC_40537811","title":"Role of DEAD/DEAH-box helicases in immunity, infection and cancers.","date":"2025","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/40537811","citation_count":10,"is_preprint":false},{"pmid":"39986544","id":"PMC_39986544","title":"Efficiently scaled-up production of recombinant human elastin-like polypeptides using multiple optimization strategies.","date":"2025","source":"Journal of biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/39986544","citation_count":10,"is_preprint":false},{"pmid":"38330300","id":"PMC_38330300","title":"Unravelling novel and pleiotropic genes for cannon bone circumference and bone mineral density in Yorkshire pigs.","date":"2024","source":"Journal of animal science","url":"https://pubmed.ncbi.nlm.nih.gov/38330300","citation_count":9,"is_preprint":false},{"pmid":"15765783","id":"PMC_15765783","title":"Refractory thrombocytopenia, an unusual myelodysplastic syndrome with an initial presentation mimicking idiopathic thrombocytopenic purpura.","date":"2005","source":"International journal of hematology","url":"https://pubmed.ncbi.nlm.nih.gov/15765783","citation_count":8,"is_preprint":false},{"pmid":"38492624","id":"PMC_38492624","title":"Circ_0007534 promotes cholangiocarcinoma stemness and resistance to anoikis through DDX3X-mediated positive feedback regulation of parental gene DDX42.","date":"2024","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/38492624","citation_count":7,"is_preprint":false},{"pmid":"30834153","id":"PMC_30834153","title":"The ATP-dependent RNA helicase, DDX42 interacts with paxillin and regulates apoptosis and polarization of Ba/F3 cells.","date":"2019","source":"Animal cells and systems","url":"https://pubmed.ncbi.nlm.nih.gov/30834153","citation_count":6,"is_preprint":false},{"pmid":"10727850","id":"PMC_10727850","title":"Identification of a novel human member of the DEAD box protein family.","date":"2000","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/10727850","citation_count":6,"is_preprint":false},{"pmid":"39372787","id":"PMC_39372787","title":"REAL-TIME VISUALIZATION OF SPLICEOSOME ASSEMBLY REVEALS BASIC PRINCIPLES OF SPLICE SITE SELECTION.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39372787","citation_count":6,"is_preprint":false},{"pmid":"39535371","id":"PMC_39535371","title":"Genetic Influence of the Brain on Muscle Structure: A Mendelian Randomization Study of Sarcopenia.","date":"2024","source":"Journal of cachexia, sarcopenia and muscle","url":"https://pubmed.ncbi.nlm.nih.gov/39535371","citation_count":4,"is_preprint":false},{"pmid":"40404675","id":"PMC_40404675","title":"Machine learning using scRNA-seq Combined with bulk-seq to identify lactylation-related hub genes in carotid arteriosclerosis.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40404675","citation_count":3,"is_preprint":false},{"pmid":"40714635","id":"PMC_40714635","title":"SUGP1 loss drives SF3B1 hotspot mutant missplicing in cancer.","date":"2025","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/40714635","citation_count":3,"is_preprint":false},{"pmid":"40790099","id":"PMC_40790099","title":"Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules.","date":"2025","source":"Endocrine","url":"https://pubmed.ncbi.nlm.nih.gov/40790099","citation_count":3,"is_preprint":false},{"pmid":"40831000","id":"PMC_40831000","title":"DDX42 Enhances Hepatocellular Carcinoma Cell Proliferation, Radiation and Sorafenib Resistance via Regulating GRB2 RNA Maturation and Activating PI3K/AKT Pathway.","date":"2025","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40831000","citation_count":2,"is_preprint":false},{"pmid":"35814901","id":"PMC_35814901","title":"miRNA-451 regulates rhesus choroid-retinal endothelial cell function and proteome profile.","date":"2022","source":"International journal of ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/35814901","citation_count":1,"is_preprint":false},{"pmid":"40849725","id":"PMC_40849725","title":"Phosphoprotein Profile of Ameloblastoma.","date":"2025","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/40849725","citation_count":0,"is_preprint":false},{"pmid":"41463182","id":"PMC_41463182","title":"Identification of Novel Susceptibility Genes for Early-Onset Colorectal Cancer Through Germline Rare Variant Burden Testing.","date":"2025","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/41463182","citation_count":0,"is_preprint":false},{"pmid":"41280439","id":"PMC_41280439","title":"Identification and experimental validation of common genes associated with both pulmonary arterial hypertension and major depressive disorder.","date":"2025","source":"Frontiers in psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/41280439","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17382,"output_tokens":2930,"usd":0.048048,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10298,"output_tokens":3260,"usd":0.066495,"stage2_stop_reason":"end_turn"},"total_usd":0.114543,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"DDX42 (SF3b125) was identified as a novel protein associated with the human 17S U2 snRNP and its stable subunit SF3b by mass spectrometry. SF3b125 dissociates at the time of 17S U2 snRNP formation, suggesting it may facilitate assembly of the 17S U2 snRNP. Immunofluorescence/FISH studies revealed SF3b125 is enriched in Cajal bodies, in contrast to SF3b155 and SF3a120, indicating a differential subnuclear distribution linked to U2 snRNP assembly.\",\n      \"method\": \"Mass spectrometry, immunodepletion, immunofluorescence/FISH\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mass spectrometry identification plus immunodepletion and localization experiments, replicated in the context of spliceosome assembly characterization\",\n      \"pmids\": [\"12234937\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Recombinant Ddx42p is an RNA-binding protein and NTPase with preference for ATP; its ATP hydrolysis is enhanced by RNA substrates. It acts as a non-processive RNA helicase, and RNA unwinding is promoted by a single-strand binding protein (T4gp32). In the ADP-bound state, Ddx42p mediates efficient annealing of complementary RNA strands and displaces the ss binding protein. Thus the adenosine nucleotide cofactor (ATP vs ADP) acts as a molecular switch controlling strand separation versus strand annealing activities.\",\n      \"method\": \"In vitro biochemical assays: NTPase assay, RNA helicase/unwinding assay, RNA annealing assay with recombinant protein\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple orthogonal in vitro enzymatic assays (NTPase, helicase, annealing) with recombinant protein in a single rigorous study\",\n      \"pmids\": [\"16397294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The N-terminus of DDX42 was identified as specifically binding to JEV NS4A protein in vitro via co-immunoprecipitation, identified using a phage display human brain cDNA library. DDX42 and JEV NS4A showed partial co-localization in human medulloblastoma TE-671 cells by confocal microscopy. Expression of N-terminal DDX42 was able to overcome JEV NS4A-induced antagonism of IFN responses.\",\n      \"method\": \"Phage display, co-immunoprecipitation, confocal microscopy, IFN reporter assay\",\n      \"journal\": \"Virus research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP and colocalization with functional rescue experiment, single lab, multiple complementary methods\",\n      \"pmids\": [\"18588927\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DDX42 was identified as a G-quadruplex (G4)-binding protein in an unbiased genome-wide shRNA screen in human cells treated with G4-stabilizing small molecules; DDX42 silencing in combination with G4 ligand treatment enhanced cell killing.\",\n      \"method\": \"Genome-wide shRNA screen, G4 ligand treatment\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genome-wide screen identified DDX42 as G4-binding, single lab, limited mechanistic follow-up on DDX42 specifically\",\n      \"pmids\": [\"31287417\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DDX42 interacts with paxillin (a focal adhesion adaptor protein) as demonstrated by reciprocal co-precipitation (His-tagged paxillin pull-down followed by anti-DDX42 western blot, and His-tagged DDX42 pull-down followed by anti-paxillin western blot). DDX42 preferentially interacts with paxillin S273A mutant over S273D mutant. DDX42 overexpression delayed IL-3 deprivation-induced apoptosis and promoted restoration of elongated cell shape in Ba/F3 cells.\",\n      \"method\": \"Ni-NTA pull-down, LC-MS, western blotting, cell morphology and apoptosis assays\",\n      \"journal\": \"Animal cells and systems\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — reciprocal pull-down with functional overexpression phenotype, single lab, two complementary methods\",\n      \"pmids\": [\"30834153\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Cancer-associated SF3B1 mutation K700E reduces interaction of DDX42 and DDX46 with SF3B1. Overexpression of DDX42 restored its decreased interaction with K700E-mutated SF3B1 and suppressed some alternative RNA splicing associated with the SF3B1 mutation. A DDX42 mutation that decreased ATP hydrolysis activity abolished the suppressive effect on alternative splicing, demonstrating that the ATP hydrolysis activity of DDX42 is required for its role in regulating RNA splicing downstream of SF3B1.\",\n      \"method\": \"Co-immunoprecipitation, overexpression, ATPase-dead mutant, splicing assays\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP, ATPase-dead mutagenesis, and splicing rescue assays, single lab\",\n      \"pmids\": [\"35652295\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX42 is an intrinsic antiviral inhibitor of HIV-1 and other positive-strand RNA viruses (CHIKV, SARS-CoV-2) and LINE-1 retrotransposition, but does not impact replication of several negative-strand RNA viruses. Depletion of endogenous DDX42 increases HIV-1 DNA accumulation and infection; overexpression inhibits infection; a dominant-negative mutant increases infection. Proximity ligation assays show DDX42 near viral elements; cross-linking RNA immunoprecipitation confirms specific interaction of DDX42 with RNAs from sensitive viruses. Recombinant DDX42 inhibits HIV-1 reverse transcription in vitro, suggesting a direct mode of action on viral ribonucleoprotein complexes.\",\n      \"method\": \"CRISPR screen, KD/KO, overexpression, dominant-negative mutant, proximity ligation assay, cross-linking RNA immunoprecipitation, in vitro reverse transcription assay, RNA-seq\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal methods including in vitro reconstitution, CLIP, proximity ligation, genetic perturbation, and dominant-negative mutagenesis in a single rigorous study\",\n      \"pmids\": [\"36161446\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Cryo-EM structures of the DDX42-SF3b complex and a DDX42-U2 snRNP assembly precursor reveal that DDX42 is anchored on SF3B1 through its N-terminal sequences, with its N-plug occupying the RNA path of SF3B1, in a binding mode strikingly analogous to DDX46. In the DDX42-U2 complex, the N-terminus remains anchored on SF3B1 but the helicase domain is displaced by U2 snRNA and TAT-SF1. In vitro assays show DDX42 and DDX46 are mutually exclusive in binding to SF3b. Cancer-driving SF3B1 mutations target residues in the RNA path that directly interact with DDX42 and DDX46.\",\n      \"method\": \"Cryo-EM structure determination, in vitro binding assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structures plus in vitro binding assays, multiple orthogonal methods establishing mechanism of U2 snRNP assembly\",\n      \"pmids\": [\"36797247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Single-molecule imaging of U2AF in vitro and in vivo established a kinetic model of splice site selection in which DDX42 helicase activity increases selectivity to the underlying U2AF binding site during spliceosome assembly, while still allowing efficient forward progression. DDX42 thus catalyzes a 'partial kinetic proofreading' mechanism for 3' splice site selection while U2AF is in complex with the spliceosome.\",\n      \"method\": \"Single-molecule fluorescence imaging in vitro and in vivo, kinetic modeling, alternative splicing analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single-molecule in vitro and in vivo imaging with mechanistic kinetic modeling, single preprint lab study\",\n      \"pmids\": [\"39372787\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX42 promotes GRB2 mRNA maturation in hepatocellular carcinoma cells, contributing to activation of the PI3K/AKT pathway, cell proliferation, and resistance to radiation and sorafenib. Knockdown of DDX42 inhibited HCC cell growth, increased radiosensitivity, enhanced sorafenib efficacy, and inactivated the PI3K/AKT pathway in vitro and in a xenograft model.\",\n      \"method\": \"Knockdown/overexpression, mRNA maturation assay, PI3K/AKT pathway readouts, subcutaneous xenograft mouse model\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss- and gain-of-function with defined pathway readout and in vivo model, single lab study\",\n      \"pmids\": [\"40831000\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DDX42 is a nuclear DEAD-box RNA helicase that functions as a component of the SF3b/17S U2 snRNP spliceosomal complex, where its N-terminus anchors to SF3B1 and its ATP hydrolysis activity regulates RNA splice site selection and suppresses aberrant splicing associated with oncogenic SF3B1 mutations; biochemically, DDX42 uses ATP vs. ADP binding as a switch between RNA strand unwinding and RNA annealing activities; beyond splicing, DDX42 acts as an intrinsic antiviral restriction factor that directly binds and inhibits positive-strand RNA viruses and retroviruses (including HIV-1, CHIKV, and SARS-CoV-2) by interacting with viral RNA and inhibiting reverse transcription, and also promotes GRB2 mRNA maturation to activate PI3K/AKT signaling in cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DDX42 is a DEAD-box RNA helicase that functions in spliceosome assembly as a component of the SF3b/17S U2 snRNP machinery and that doubles as an intrinsic antiviral restriction factor [#0, #6]. It was first identified as SF3b125, a protein associated with the human 17S U2 snRNP and its stable SF3b core that dissociates upon mature 17S U2 snRNP formation and is enriched in Cajal bodies, marking it as an assembly factor [#0]. Cryo-EM structures show DDX42 anchored on SF3B1 through its N-terminal sequences, with its N-plug occupying the SF3B1 RNA path in a binding mode analogous to and mutually exclusive with DDX46; upon U2 snRNP assembly the N-terminus remains anchored while the helicase domain is displaced by U2 snRNA and TAT-SF1 [#7]. As an enzyme, DDX42 is an RNA-stimulated NTPase that uses ATP versus ADP binding as a molecular switch between non-processive RNA strand unwinding and RNA annealing [#1], and its ATP hydrolysis activity is required to suppress aberrant alternative splicing caused by oncogenic SF3B1-K700E, which weakens the DDX42-SF3B1 interaction [#5]. Independently of splicing, DDX42 directly binds the RNA of positive-strand RNA viruses and retroviruses (HIV-1, CHIKV, SARS-CoV-2) and LINE-1 elements and inhibits HIV-1 reverse transcription in vitro, acting on viral ribonucleoprotein complexes [#6]. In cancer cells DDX42 promotes GRB2 mRNA maturation to activate PI3K/AKT signaling and drive proliferation and therapy resistance [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Establishing that DDX42 (SF3b125) is a U2 snRNP-associated factor placed it within the spliceosome assembly pathway rather than the mature snRNP.\",\n      \"evidence\": \"Mass spectrometry, immunodepletion, and immunofluorescence/FISH on human 17S U2 snRNP/SF3b\",\n      \"pmids\": [\"12234937\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the molecular contacts anchoring DDX42 to SF3b\", \"Functional role in assembly inferred from dissociation timing, not directly tested\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Biochemical reconstitution defined DDX42 as an RNA-stimulated NTPase whose nucleotide state switches it between unwinding and annealing, giving the protein a defined enzymatic logic.\",\n      \"evidence\": \"In vitro NTPase, helicase, and RNA annealing assays with recombinant protein\",\n      \"pmids\": [\"16397294\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological RNA substrates not identified\", \"Link between in vitro switch and spliceosome function not established\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Identification of an interaction with JEV NS4A and rescue of IFN antagonism hinted at an antiviral/immune-modulatory role beyond splicing.\",\n      \"evidence\": \"Phage display, co-immunoprecipitation, confocal colocalization, IFN reporter assay in TE-671 cells\",\n      \"pmids\": [\"18588927\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, in vitro co-IP without endogenous validation\", \"Mechanism connecting DDX42 N-terminus to IFN response unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Unbiased screens linked DDX42 to G-quadruplex RNA/DNA biology and to a focal adhesion adaptor, broadening its candidate interaction landscape.\",\n      \"evidence\": \"Genome-wide shRNA screen with G4 ligands; reciprocal Ni-NTA pull-down with paxillin plus morphology/apoptosis assays\",\n      \"pmids\": [\"31287417\", \"30834153\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"G4 binding by DDX42 not directly demonstrated biochemically\", \"Paxillin interaction lacks mechanistic context or endogenous confirmation\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linking ATP-hydrolysis-dependent DDX42 activity to suppression of SF3B1-mutant aberrant splicing connected its enzymatic switch to oncogenic spliceosome dysfunction.\",\n      \"evidence\": \"Co-IP, overexpression rescue, ATPase-dead mutant, and splicing assays in cells with SF3B1-K700E\",\n      \"pmids\": [\"35652295\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct RNA targets of the splicing-suppressive activity not mapped\", \"Single lab, no structural basis at this stage\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrating direct viral RNA binding and inhibition of reverse transcription established DDX42 as a genuine intrinsic antiviral restriction factor with selectivity for positive-strand RNA viruses and retroelements.\",\n      \"evidence\": \"CRISPR screen, KD/KO, overexpression, dominant-negative mutant, PLA, CLIP, in vitro reverse transcription assay, RNA-seq\",\n      \"pmids\": [\"36161446\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether antiviral and splicing roles use the same domains/activity unresolved\", \"Basis for virus selectivity not fully defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Cryo-EM structures revealed how DDX42 docks onto SF3B1 via its N-plug and how cancer mutations and DDX46 competition map to the same RNA path, providing the structural mechanism of U2 snRNP assembly.\",\n      \"evidence\": \"Cryo-EM of DDX42-SF3b and DDX42-U2 snRNP precursor plus in vitro binding assays\",\n      \"pmids\": [\"36797247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of DDX42/DDX46 exchange during assembly not kinetically resolved\", \"Helicase domain displacement role in catalysis not directly tested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Single-molecule kinetics framed DDX42 helicase activity as a partial kinetic proofreading mechanism that tunes 3' splice site selectivity at U2AF.\",\n      \"evidence\": \"Single-molecule fluorescence imaging of U2AF in vitro and in vivo with kinetic modeling (preprint)\",\n      \"pmids\": [\"39372787\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Quantitative model awaits independent confirmation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showing DDX42 promotes GRB2 mRNA maturation to drive PI3K/AKT signaling tied its RNA-processing activity to cancer proliferation and therapy resistance.\",\n      \"evidence\": \"Knockdown/overexpression, mRNA maturation assay, PI3K/AKT readouts, and xenograft model in HCC cells\",\n      \"pmids\": [\"40831000\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of DDX42 to GRB2 transcript not structurally defined\", \"Single lab; generality across cancer types untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DDX42's helicase enzymology is partitioned and coordinated across its splicing, antiviral, and oncogenic mRNA-maturation roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model relating ATP-switch activity to substrate choice across contexts\", \"Whether nuclear splicing and cytoplasmic/viral functions reflect distinct pools is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1, 6]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016787\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\n      \"SF3b\",\n      \"17S U2 snRNP\"\n    ],\n    \"partners\": [\n      \"SF3B1\",\n      \"DDX46\",\n      \"TAT-SF1\",\n      \"U2AF\",\n      \"PXN\",\n      \"JEV NS4A\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}