{"gene":"DDX52","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":1995,"finding":"ROK1 encodes an essential yeast protein containing conserved DEAD-box domains characteristic of ATP-dependent RNA helicases; it was identified as a high-copy suppressor of the kem1 null mutation.","method":"Sequence analysis, genetic suppressor screen, viability assays","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — sequence-based classification plus genetic suppression, replicated in subsequent biochemical studies","pmids":["8529880"],"is_preprint":false},{"year":1998,"finding":"Rok1 protein (~64 kDa) is localized predominantly to the cytoplasm in vegetatively growing Saccharomyces cerevisiae cells, as determined by indirect immunofluorescence with affinity-purified anti-Rok1 antibodies.","method":"Western blot, indirect immunofluorescence","journal":"Molecules and cells","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single localization method, no functional consequence linked","pmids":["9571634"],"is_preprint":false},{"year":1999,"finding":"Rok1 possesses intrinsic ATPase activity, and mutations in conserved ATPase motifs abolish this activity and cause in vivo lethality, demonstrating that ATP hydrolysis is essential for Rok1 function. Notably, the ATPase activity is RNA-independent.","method":"In vitro ATPase assay with purified MBP-Rok1 fusion protein, site-directed mutagenesis, in vivo lethality tests","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay combined with mutagenesis and in vivo functional validation in a single focused study","pmids":["10373593"],"is_preprint":false},{"year":2008,"finding":"The DEAD-box helicase Rok1 is specifically required for release of the essential snoRNA snR30 from pre-ribosomes during 40S subunit synthesis. Point mutations in helicase motif I impair snR30 release, while motif III mutations do not, indicating mechanistic specificity of different helicase motifs.","method":"Quantitative snoRNA association screen (Northern blot-based), helicase domain point mutations, yeast depletion strains","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic quantitative screen across 75 snoRNAs with multiple domain mutants, replicated conceptually in subsequent studies","pmids":["18833290"],"is_preprint":false},{"year":2010,"finding":"Rok1 protein levels oscillate during the yeast cell cycle (declining at G1/S, increasing at G2), controlled by two upstream open reading frames (uORFs) in the ROK1 5'-UTR that inhibit translation. Disrupting uORFs elevates Rok1 levels and causes delays in bud emergence and recovery from pheromone arrest.","method":"uORF mutagenesis, Western blot cell-cycle analysis, pheromone arrest/release assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic mutagenesis with functional cell cycle readout, single lab","pmids":["20969870"],"is_preprint":false},{"year":2014,"finding":"UV cross-linking (CRAC) revealed that Rok1 directly contacts pre-rRNA at multiple sites clustering in the 'foot' region of the small ribosomal subunit, particularly the expansion segment ES6, where it promotes snR30 release. CLASH further identified novel pre-rRNA base-pairing sites for snR30, snR10, U3, and U14 clustering in expansion segments, suggesting these snoRNAs bridge long-range rRNA interactions during early ribosome assembly.","method":"UV cross-linking and analysis of cDNA (CRAC), cross-linking ligation and sequencing of hybrids (CLASH)","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — two orthogonal UV cross-linking methods with nucleotide-resolution mapping in a single focused study","pmids":["24947498"],"is_preprint":false},{"year":2015,"finding":"Three ROK1 5'-UTR-binding proteins—Psk2 (PAS kinase), Skp1, and Tub4—regulate Rok1 translation through uORF1: Psk2 and Skp1 repress Rok1 synthesis, while Tub4 promotes it, acting downstream of uORF1-mediated inhibition.","method":"Yeast three-hybrid screening, PSK2 deletion analysis, temperature-sensitive alleles of SKP1 and TUB4","journal":"Journal of microbiology (Seoul, Korea)","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — three-hybrid binding plus genetic deletion/ts-allele functional tests, single lab with multiple trans-factors","pmids":["26310304"],"is_preprint":false},{"year":2016,"finding":"ATP-bound (but not ADP-bound) Rok1 stabilizes Rrp5 binding to pre-40S ribosomes, and ATP hydrolysis by Rok1 is required to release Rrp5 from pre-40S ribosomes in vivo, freeing Rrp5 to participate in 60S subunit assembly. Blocked Rrp5 release causes secondary accumulation of snR30. An interaction between Rrp5 and the DEAD-box protein Has1 is implicated in snR30 accumulation when Rrp5 release is blocked.","method":"In vivo and in vitro biochemical analyses, ATP/ADP-form Rok1 binding assays, Rrp5 co-immunoprecipitation, functional epistasis","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of nucleotide-state-dependent binding combined with in vivo functional epistasis and co-IP, single lab but multiple orthogonal methods","pmids":["27280440"],"is_preprint":false},{"year":2021,"finding":"Ddx52 (the zebrafish ortholog of DDX52) maintains the level of 47S precursor ribosomal RNA and is essential for juvenile growth; loss-of-function by temperature-sensitive mutation suspends whole-organism growth reversibly.","method":"Forward genetic screen, positional cloning, complementation assays, 47S pre-rRNA quantification","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic cloning with pre-rRNA molecular readout in vivo, single lab","pmids":["34323273"],"is_preprint":false},{"year":2021,"finding":"DDX52 knockdown in prostate cancer cells inhibits cell growth in vitro and in vivo, and suppresses c-Myc signaling; conversely, c-Myc transcriptionally regulates DDX52 expression, forming a positive feedback loop.","method":"shRNA knockdown, RNA sequencing, GSEA, Western blot, xenograft mouse model, IHC","journal":"Cancer cell international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — shRNA KD with phenotype and pathway inference, no direct biochemical mechanism established, single lab","pmids":["34399732"],"is_preprint":false},{"year":2021,"finding":"DDX52 knockdown suppresses melanoma cell proliferation and tumor growth, and an RNA immunoprecipitation assay confirmed physical association between DDX52 protein and c-Myc mRNA; restoration of c-Myc partly rescues DDX52-deficiency phenotypes.","method":"shRNA knockdown, RNA immunoprecipitation (RIP), xenograft mouse model, rescue assay","journal":"Bioengineered","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — RIP confirms direct DDX52–c-Myc mRNA interaction, supported by rescue experiment; single lab","pmids":["34233596"],"is_preprint":false},{"year":2022,"finding":"In Drosophila, Rok1 and its cofactor Rrp5 co-localize to the nucleolus and are both required for pre-rRNA processing and ribosome assembly. Loss of Rok1 causes nucleolar enlargement, stalled ribosome assembly, and inhibition of mitosis in the brain. Rok1 depletion also mislocalizes Rrp5 within the nucleolus, suggesting Rok1 is required for accurate Rrp5 positioning.","method":"Genetics (mutant analysis), fluorescence in situ hybridization (FISH), developmental phenotype assays","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic loss-of-function with nucleolar localization and pre-rRNA processing readouts in a multicellular organism, single lab","pmids":["35628496"],"is_preprint":false},{"year":2026,"finding":"Human DDX52 is an ATP-dependent 3'-to-5' translocase/helicase that can unwind DNA duplexes and DNA/RNA hybrids in vitro. DDX52 also functions as a nucleic acid annealase (strand annealing), an activity that requires the N-terminal intrinsically disordered region (IDR) and becomes hyperactive when helicase activity is abolished by mutagenesis. CRISPR-generated DDX52+/- U2OS cells exhibit growth defects and impaired cell migration.","method":"In vitro helicase/translocase assay, strand-annealing assay, helicase-dead mutagenesis, CRISPR-Cas9 heterozygous knockout, cell migration assay","journal":"Bioscience reports","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple in vitro enzymatic assays with mutagenesis plus CRISPR-based cellular phenotypes, single lab but orthogonal methods","pmids":["41510705"],"is_preprint":false},{"year":2026,"finding":"In fission yeast, rok1 deletion shortens and slows actin ring contraction during cytokinesis and inhibits kinetochore separation during mitosis. Transcriptomic analysis identified upregulation of myo51 and blt1 (delaying actin ring assembly) and psm3/psc3 cohesin subunits as key downstream effectors of Rok1 deletion phenotypes.","method":"Fluorescent protein labeling, live-cell imaging, RNA sequencing, bioinformatics","journal":"Experimental and therapeutic medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — live imaging with transcriptomic inferences; mechanistic pathway not directly validated by rescue or biochemistry","pmids":["42016605"],"is_preprint":false}],"current_model":"DDX52/Rok1 is an essential ATP-dependent DEAD-box RNA helicase whose ATPase activity (RNA-independent in vitro) drives remodeling of pre-ribosomal complexes: ATP-bound Rok1 stabilizes the cofactor Rrp5 on pre-40S ribosomes, ATP hydrolysis releases Rrp5 to allow 60S assembly, and this remodeling is mechanistically linked to displacement of the essential snoRNA snR30 from expansion segment ES6 of pre-18S rRNA where Rok1 directly cross-links; in human cells DDX52 additionally acts as a 3'-5' ATP-dependent DNA/RNA helicase and strand annealase (the latter requiring its N-terminal IDR), and heterozygous CRISPR knockout causes growth and cell-migration defects, with DDX52 physically associating with c-Myc mRNA to support c-Myc-dependent oncogenic signaling."},"narrative":{"mechanistic_narrative":"DDX52 (yeast Rok1) is an essential ATP-dependent DEAD-box RNA helicase that drives remodeling of pre-ribosomal complexes during small-subunit biogenesis [PMID:8529880, PMID:10373593, PMID:18833290]. Its intrinsic ATPase activity is RNA-independent in vitro, and mutation of conserved ATPase motifs abolishes catalysis and causes lethality, establishing ATP hydrolysis as the core of its function [PMID:10373593]. Mechanistically, Rok1 is specifically required to release the essential snoRNA snR30 from pre-ribosomes, with distinct helicase motifs contributing unequally to this step, and it directly cross-links to pre-rRNA at expansion segment ES6 in the 'foot' of the small subunit where snR30 base-pairs [PMID:18833290, PMID:24947498]. Nucleotide state couples this remodeling to the cofactor Rrp5: ATP-bound Rok1 stabilizes Rrp5 on pre-40S ribosomes while ATP hydrolysis releases Rrp5 to permit 60S assembly, and Rok1 is also required for accurate Rrp5 positioning in the nucleolus [PMID:27280440, PMID:35628496]. The ribosome-biogenesis role is conserved across species, supporting 47S pre-rRNA maintenance and growth in zebrafish and pre-rRNA processing with mitotic progression in Drosophila [PMID:34323273, PMID:35628496]. Human DDX52 acts as an ATP-dependent 3'-to-5' translocase that unwinds DNA duplexes and DNA/RNA hybrids and, conversely, possesses an annealase activity that depends on its N-terminal intrinsically disordered region and is hyperactive when helicase activity is disabled [PMID:41510705]. In human cancer cells, DDX52 physically associates with c-Myc mRNA and supports c-Myc-dependent oncogenic signaling, with knockdown suppressing tumor growth [PMID:34233596].","teleology":[{"year":1995,"claim":"Established that ROK1 encodes an essential DEAD-box helicase, placing it in the ATP-dependent RNA helicase class before any biochemical activity was known.","evidence":"Sequence analysis and genetic suppressor screen of the kem1 null in yeast","pmids":["8529880"],"confidence":"Medium","gaps":["No enzymatic activity demonstrated","No substrate or pathway assigned","Functional link to kem1 mechanism unresolved"]},{"year":1998,"claim":"Determined the subcellular distribution of Rok1, providing the first spatial context for its activity.","evidence":"Indirect immunofluorescence with affinity-purified anti-Rok1 antibodies in S. cerevisiae","pmids":["9571634"],"confidence":"Medium","gaps":["Single localization method, no functional consequence","Cytoplasmic signal does not address nucleolar pool seen in later orthologs"]},{"year":1999,"claim":"Showed that ATP hydrolysis is the essential catalytic core of Rok1 function, and unexpectedly that its ATPase is RNA-independent in vitro.","evidence":"In vitro ATPase assay with purified MBP-Rok1, ATPase-motif mutagenesis, and in vivo lethality tests","pmids":["10373593"],"confidence":"High","gaps":["RNA substrate that activates ATPase in vivo not identified","No structural basis for RNA-independence"]},{"year":2008,"claim":"Pinpointed Rok1's specific substrate step in ribosome assembly—release of snR30—and revealed functional non-equivalence among helicase motifs.","evidence":"Quantitative snoRNA-association screen across 75 snoRNAs with motif I/III point mutants in yeast depletion strains","pmids":["18833290"],"confidence":"High","gaps":["Direct rRNA contact site not yet mapped","Whether release is direct unwinding or remodeling unclear"]},{"year":2014,"claim":"Localized Rok1's direct pre-rRNA contacts to expansion segment ES6 in the subunit foot, providing nucleotide-resolution evidence for where it acts on snR30.","evidence":"CRAC and CLASH UV cross-linking mapping in yeast","pmids":["24947498"],"confidence":"High","gaps":["Does not establish catalytic order relative to Rrp5","Functional consequence of each cross-link site untested"]},{"year":2016,"claim":"Defined a nucleotide-state cycle in which ATP-bound Rok1 stabilizes Rrp5 and hydrolysis releases it, mechanistically coupling 40S remodeling to downstream 60S assembly.","evidence":"In vitro ATP/ADP-form binding assays, Rrp5 co-IP, and in vivo functional epistasis in yeast","pmids":["27280440"],"confidence":"High","gaps":["Structural model of the Rok1-Rrp5-pre40S complex absent","Trigger for ATP hydrolysis in vivo unknown"]},{"year":2021,"claim":"Demonstrated conservation of the ribosome-biogenesis role in a vertebrate, linking DDX52 to 47S pre-rRNA maintenance and organismal growth.","evidence":"Forward genetic screen, positional cloning, and 47S pre-rRNA quantification in zebrafish","pmids":["34323273"],"confidence":"Medium","gaps":["Molecular step in vertebrate processing not resolved","snR30 ortholog dependence not tested"]},{"year":2021,"claim":"Connected DDX52 to c-Myc oncogenic signaling, including direct binding to c-Myc mRNA, extending its biology to cancer cell proliferation.","evidence":"shRNA knockdown, RNA immunoprecipitation, xenografts, and c-Myc rescue in melanoma and prostate cancer cells","pmids":["34233596","34399732"],"confidence":"Medium","gaps":["Whether c-Myc mRNA effect is via helicase activity untested","Relationship to ribosome biogenesis role in tumors unclear","c-Myc transcriptional feedback inferred from knockdown only"]},{"year":2022,"claim":"Confirmed nucleolar co-localization and co-dependence of Rok1 and Rrp5 in a multicellular animal and tied Rok1 loss to mitotic arrest, reinforcing the conserved assembly mechanism.","evidence":"Drosophila mutant genetics, FISH, and developmental phenotyping","pmids":["35628496"],"confidence":"Medium","gaps":["Mitotic defect may be indirect consequence of stalled biogenesis","Direct Rrp5 interaction not biochemically shown in fly"]},{"year":2026,"claim":"Resolved the human enzyme's biochemical repertoire, showing it is a 3'-5' translocase that unwinds DNA and DNA/RNA hybrids and also anneals strands via its N-terminal IDR, expanding its activity beyond canonical RNA remodeling.","evidence":"In vitro helicase/translocase and annealing assays, helicase-dead mutagenesis, and CRISPR heterozygous knockout phenotyping in U2OS cells","pmids":["41510705"],"confidence":"High","gaps":["Physiological substrate of DNA/hybrid unwinding unknown","How annealase vs helicase activity is regulated in cells unresolved","Link between in vitro activities and migration/growth phenotype not established"]},{"year":2026,"claim":"Implicated Rok1 in cytokinesis and chromosome segregation in fission yeast through transcriptomic effectors, broadening its phenotypic footprint.","evidence":"Live-cell imaging of actin ring and kinetochores plus RNA sequencing in S. pombe rok1 deletion","pmids":["42016605"],"confidence":"Low","gaps":["Downstream effectors inferred from transcriptomics without rescue validation","Direct mechanistic link to helicase activity not established","May reflect indirect consequence of ribosome biogenesis defect"]},{"year":null,"claim":"How DDX52's biochemically defined DNA/RNA unwinding and annealase activities relate mechanistically to its established role in pre-ribosome remodeling and to c-Myc-dependent oncogenesis remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No physiological substrate linking helicase/annealase activities to ribosome assembly","No structural model of the human enzyme on substrate","Mechanism connecting DDX52 to c-Myc mRNA fate undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[2,7,12]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,5,10]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[3,5]},{"term_id":"GO:0140097","term_label":"catalytic activity, acting on DNA","supporting_discovery_ids":[12]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[12]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[11]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3,5,7,8]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[7,8,11]}],"complexes":["pre-40S ribosome"],"partners":["RRP5","SNR30"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y2R4","full_name":"Probable ATP-dependent RNA helicase DDX52","aliases":["ATP-dependent RNA helicase ROK1-like","DEAD box protein 52"],"length_aa":599,"mass_kda":67.5,"function":"Required for efficient ribosome biogenesis (By similarity). May control cell cycle progression by regulating translation of mRNAs that contain a terminal oligo pyrimidine (TOP) motif in their 5' UTRs, such as GTPBP4 (By similarity)","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9Y2R4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DDX52","classification":"Common Essential","n_dependent_lines":951,"n_total_lines":1208,"dependency_fraction":0.7872516556291391},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"FKBP5","stoichiometry":0.2},{"gene":"PTGES3","stoichiometry":0.2},{"gene":"PTMA","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DDX52","total_profiled":1310},"omim":[{"mim_id":"612500","title":"DExD-BOX HELICASE 52; DDX52","url":"https://www.omim.org/entry/612500"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DDX52"},"hgnc":{"alias_symbol":["ROK1"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y2R4","domains":[{"cath_id":"3.40.50.300","chopping":"133-377","consensus_level":"high","plddt":88.0153,"start":133,"end":377},{"cath_id":"3.40.50.300","chopping":"387-559","consensus_level":"high","plddt":87.0053,"start":387,"end":559}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2R4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2R4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2R4-F1-predicted_aligned_error_v6.png","plddt_mean":76.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DDX52","jax_strain_url":"https://www.jax.org/strain/search?query=DDX52"},"sequence":{"accession":"Q9Y2R4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y2R4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y2R4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2R4"}},"corpus_meta":[{"pmid":"18833290","id":"PMC_18833290","title":"Quantitative analysis of snoRNA association with pre-ribosomes and release of snR30 by Rok1 helicase.","date":"2008","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/18833290","citation_count":65,"is_preprint":false},{"pmid":"24947498","id":"PMC_24947498","title":"A pre-ribosomal RNA interaction network involving snoRNAs and the Rok1 helicase.","date":"2014","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/24947498","citation_count":42,"is_preprint":false},{"pmid":"27280440","id":"PMC_27280440","title":"The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation.","date":"2016","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/27280440","citation_count":38,"is_preprint":false},{"pmid":"19486294","id":"PMC_19486294","title":"The dual specificity phosphatase Rok1 negatively regulates mating and pathogenicity in Ustilago maydis.","date":"2009","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/19486294","citation_count":30,"is_preprint":false},{"pmid":"10373593","id":"PMC_10373593","title":"ATP hydrolysis activity of the DEAD box protein Rok1p is required for in vivo ROK1 function.","date":"1999","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/10373593","citation_count":23,"is_preprint":false},{"pmid":"8529880","id":"PMC_8529880","title":"ROK1, a high-copy-number plasmid suppressor of kem1, encodes a putative ATP-dependent RNA helicase in Saccharomyces cerevisiae.","date":"1995","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8529880","citation_count":23,"is_preprint":false},{"pmid":"34323273","id":"PMC_34323273","title":"The RNA helicase Ddx52 functions as a growth switch in juvenile zebrafish.","date":"2021","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/34323273","citation_count":11,"is_preprint":false},{"pmid":"20969870","id":"PMC_20969870","title":"Upstream open reading frames regulate the cell cycle-dependent expression of the RNA helicase Rok1 in Saccharomyces cerevisiae.","date":"2010","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/20969870","citation_count":10,"is_preprint":false},{"pmid":"31848283","id":"PMC_31848283","title":"The Unfolded Protein Response Regulates Pathogenic Development of Ustilago maydis by Rok1-Dependent Inhibition of Mating-Type Signaling.","date":"2019","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/31848283","citation_count":9,"is_preprint":false},{"pmid":"34399732","id":"PMC_34399732","title":"DDX52 knockdown inhibits the growth of prostate cancer cells by regulating c-Myc signaling.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/34399732","citation_count":9,"is_preprint":false},{"pmid":"29288727","id":"PMC_29288727","title":"Characterization of the Es-DDX52 involved in the spermatogonial mitosis and spermatid differentiation in Chinese mitten crab (Eriocheir sinensis).","date":"2017","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/29288727","citation_count":8,"is_preprint":false},{"pmid":"34233596","id":"PMC_34233596","title":"Knockdown of DEAD-box RNA helicase 52 (DDX52) suppresses the proliferation of melanoma cells in vitro and of nude mouse xenografts by targeting c-Myc.","date":"2021","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34233596","citation_count":7,"is_preprint":false},{"pmid":"10705369","id":"PMC_10705369","title":"Identification of a putative DEAD-box RNA helicase and a zinc-finger protein in Candida albicans by functional complementation of the S. cerevisiae rok1 mutation.","date":"2000","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/10705369","citation_count":7,"is_preprint":false},{"pmid":"9571634","id":"PMC_9571634","title":"Characterization and intracellular localization of the Rok1 protein involved in yeast cell division.","date":"1998","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/9571634","citation_count":4,"is_preprint":false},{"pmid":"26310304","id":"PMC_26310304","title":"Identification of Psk2, Skp1, and Tub4 as trans-acting factors for uORF-containing ROK1 mRNA in Saccharomyces cerevisiae.","date":"2015","source":"Journal of microbiology (Seoul, Korea)","url":"https://pubmed.ncbi.nlm.nih.gov/26310304","citation_count":4,"is_preprint":false},{"pmid":"35628496","id":"PMC_35628496","title":"The DEAD-Box Protein Rok1 Coordinates Ribosomal RNA Processing in Association with Rrp5 in Drosophila.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35628496","citation_count":1,"is_preprint":false},{"pmid":"41510705","id":"PMC_41510705","title":"The human DDX52 protein is a nucleic acid helicase and strand annealase that promotes cell migration.","date":"2026","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/41510705","citation_count":0,"is_preprint":false},{"pmid":"42016605","id":"PMC_42016605","title":"Effects of rok1 gene deletion on mitosis in fission yeast at appropriate and stressful temperatures and the molecular mechanisms.","date":"2026","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/42016605","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9898,"output_tokens":3360,"usd":0.040047,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10960,"output_tokens":3693,"usd":0.073563,"stage2_stop_reason":"end_turn"},"total_usd":0.11361,"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\": 1995,\n      \"finding\": \"ROK1 encodes an essential yeast protein containing conserved DEAD-box domains characteristic of ATP-dependent RNA helicases; it was identified as a high-copy suppressor of the kem1 null mutation.\",\n      \"method\": \"Sequence analysis, genetic suppressor screen, viability assays\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — sequence-based classification plus genetic suppression, replicated in subsequent biochemical studies\",\n      \"pmids\": [\"8529880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Rok1 protein (~64 kDa) is localized predominantly to the cytoplasm in vegetatively growing Saccharomyces cerevisiae cells, as determined by indirect immunofluorescence with affinity-purified anti-Rok1 antibodies.\",\n      \"method\": \"Western blot, indirect immunofluorescence\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single localization method, no functional consequence linked\",\n      \"pmids\": [\"9571634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Rok1 possesses intrinsic ATPase activity, and mutations in conserved ATPase motifs abolish this activity and cause in vivo lethality, demonstrating that ATP hydrolysis is essential for Rok1 function. Notably, the ATPase activity is RNA-independent.\",\n      \"method\": \"In vitro ATPase assay with purified MBP-Rok1 fusion protein, site-directed mutagenesis, in vivo lethality tests\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay combined with mutagenesis and in vivo functional validation in a single focused study\",\n      \"pmids\": [\"10373593\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The DEAD-box helicase Rok1 is specifically required for release of the essential snoRNA snR30 from pre-ribosomes during 40S subunit synthesis. Point mutations in helicase motif I impair snR30 release, while motif III mutations do not, indicating mechanistic specificity of different helicase motifs.\",\n      \"method\": \"Quantitative snoRNA association screen (Northern blot-based), helicase domain point mutations, yeast depletion strains\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic quantitative screen across 75 snoRNAs with multiple domain mutants, replicated conceptually in subsequent studies\",\n      \"pmids\": [\"18833290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Rok1 protein levels oscillate during the yeast cell cycle (declining at G1/S, increasing at G2), controlled by two upstream open reading frames (uORFs) in the ROK1 5'-UTR that inhibit translation. Disrupting uORFs elevates Rok1 levels and causes delays in bud emergence and recovery from pheromone arrest.\",\n      \"method\": \"uORF mutagenesis, Western blot cell-cycle analysis, pheromone arrest/release assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic mutagenesis with functional cell cycle readout, single lab\",\n      \"pmids\": [\"20969870\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"UV cross-linking (CRAC) revealed that Rok1 directly contacts pre-rRNA at multiple sites clustering in the 'foot' region of the small ribosomal subunit, particularly the expansion segment ES6, where it promotes snR30 release. CLASH further identified novel pre-rRNA base-pairing sites for snR30, snR10, U3, and U14 clustering in expansion segments, suggesting these snoRNAs bridge long-range rRNA interactions during early ribosome assembly.\",\n      \"method\": \"UV cross-linking and analysis of cDNA (CRAC), cross-linking ligation and sequencing of hybrids (CLASH)\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — two orthogonal UV cross-linking methods with nucleotide-resolution mapping in a single focused study\",\n      \"pmids\": [\"24947498\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Three ROK1 5'-UTR-binding proteins—Psk2 (PAS kinase), Skp1, and Tub4—regulate Rok1 translation through uORF1: Psk2 and Skp1 repress Rok1 synthesis, while Tub4 promotes it, acting downstream of uORF1-mediated inhibition.\",\n      \"method\": \"Yeast three-hybrid screening, PSK2 deletion analysis, temperature-sensitive alleles of SKP1 and TUB4\",\n      \"journal\": \"Journal of microbiology (Seoul, Korea)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — three-hybrid binding plus genetic deletion/ts-allele functional tests, single lab with multiple trans-factors\",\n      \"pmids\": [\"26310304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ATP-bound (but not ADP-bound) Rok1 stabilizes Rrp5 binding to pre-40S ribosomes, and ATP hydrolysis by Rok1 is required to release Rrp5 from pre-40S ribosomes in vivo, freeing Rrp5 to participate in 60S subunit assembly. Blocked Rrp5 release causes secondary accumulation of snR30. An interaction between Rrp5 and the DEAD-box protein Has1 is implicated in snR30 accumulation when Rrp5 release is blocked.\",\n      \"method\": \"In vivo and in vitro biochemical analyses, ATP/ADP-form Rok1 binding assays, Rrp5 co-immunoprecipitation, functional epistasis\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of nucleotide-state-dependent binding combined with in vivo functional epistasis and co-IP, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"27280440\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Ddx52 (the zebrafish ortholog of DDX52) maintains the level of 47S precursor ribosomal RNA and is essential for juvenile growth; loss-of-function by temperature-sensitive mutation suspends whole-organism growth reversibly.\",\n      \"method\": \"Forward genetic screen, positional cloning, complementation assays, 47S pre-rRNA quantification\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic cloning with pre-rRNA molecular readout in vivo, single lab\",\n      \"pmids\": [\"34323273\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DDX52 knockdown in prostate cancer cells inhibits cell growth in vitro and in vivo, and suppresses c-Myc signaling; conversely, c-Myc transcriptionally regulates DDX52 expression, forming a positive feedback loop.\",\n      \"method\": \"shRNA knockdown, RNA sequencing, GSEA, Western blot, xenograft mouse model, IHC\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — shRNA KD with phenotype and pathway inference, no direct biochemical mechanism established, single lab\",\n      \"pmids\": [\"34399732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DDX52 knockdown suppresses melanoma cell proliferation and tumor growth, and an RNA immunoprecipitation assay confirmed physical association between DDX52 protein and c-Myc mRNA; restoration of c-Myc partly rescues DDX52-deficiency phenotypes.\",\n      \"method\": \"shRNA knockdown, RNA immunoprecipitation (RIP), xenograft mouse model, rescue assay\",\n      \"journal\": \"Bioengineered\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — RIP confirms direct DDX52–c-Myc mRNA interaction, supported by rescue experiment; single lab\",\n      \"pmids\": [\"34233596\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Drosophila, Rok1 and its cofactor Rrp5 co-localize to the nucleolus and are both required for pre-rRNA processing and ribosome assembly. Loss of Rok1 causes nucleolar enlargement, stalled ribosome assembly, and inhibition of mitosis in the brain. Rok1 depletion also mislocalizes Rrp5 within the nucleolus, suggesting Rok1 is required for accurate Rrp5 positioning.\",\n      \"method\": \"Genetics (mutant analysis), fluorescence in situ hybridization (FISH), developmental phenotype assays\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic loss-of-function with nucleolar localization and pre-rRNA processing readouts in a multicellular organism, single lab\",\n      \"pmids\": [\"35628496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Human DDX52 is an ATP-dependent 3'-to-5' translocase/helicase that can unwind DNA duplexes and DNA/RNA hybrids in vitro. DDX52 also functions as a nucleic acid annealase (strand annealing), an activity that requires the N-terminal intrinsically disordered region (IDR) and becomes hyperactive when helicase activity is abolished by mutagenesis. CRISPR-generated DDX52+/- U2OS cells exhibit growth defects and impaired cell migration.\",\n      \"method\": \"In vitro helicase/translocase assay, strand-annealing assay, helicase-dead mutagenesis, CRISPR-Cas9 heterozygous knockout, cell migration assay\",\n      \"journal\": \"Bioscience reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple in vitro enzymatic assays with mutagenesis plus CRISPR-based cellular phenotypes, single lab but orthogonal methods\",\n      \"pmids\": [\"41510705\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In fission yeast, rok1 deletion shortens and slows actin ring contraction during cytokinesis and inhibits kinetochore separation during mitosis. Transcriptomic analysis identified upregulation of myo51 and blt1 (delaying actin ring assembly) and psm3/psc3 cohesin subunits as key downstream effectors of Rok1 deletion phenotypes.\",\n      \"method\": \"Fluorescent protein labeling, live-cell imaging, RNA sequencing, bioinformatics\",\n      \"journal\": \"Experimental and therapeutic medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — live imaging with transcriptomic inferences; mechanistic pathway not directly validated by rescue or biochemistry\",\n      \"pmids\": [\"42016605\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DDX52/Rok1 is an essential ATP-dependent DEAD-box RNA helicase whose ATPase activity (RNA-independent in vitro) drives remodeling of pre-ribosomal complexes: ATP-bound Rok1 stabilizes the cofactor Rrp5 on pre-40S ribosomes, ATP hydrolysis releases Rrp5 to allow 60S assembly, and this remodeling is mechanistically linked to displacement of the essential snoRNA snR30 from expansion segment ES6 of pre-18S rRNA where Rok1 directly cross-links; in human cells DDX52 additionally acts as a 3'-5' ATP-dependent DNA/RNA helicase and strand annealase (the latter requiring its N-terminal IDR), and heterozygous CRISPR knockout causes growth and cell-migration defects, with DDX52 physically associating with c-Myc mRNA to support c-Myc-dependent oncogenic signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DDX52 (yeast Rok1) is an essential ATP-dependent DEAD-box RNA helicase that drives remodeling of pre-ribosomal complexes during small-subunit biogenesis [#0, #2, #3]. Its intrinsic ATPase activity is RNA-independent in vitro, and mutation of conserved ATPase motifs abolishes catalysis and causes lethality, establishing ATP hydrolysis as the core of its function [#2]. Mechanistically, Rok1 is specifically required to release the essential snoRNA snR30 from pre-ribosomes, with distinct helicase motifs contributing unequally to this step, and it directly cross-links to pre-rRNA at expansion segment ES6 in the 'foot' of the small subunit where snR30 base-pairs [#3, #5]. Nucleotide state couples this remodeling to the cofactor Rrp5: ATP-bound Rok1 stabilizes Rrp5 on pre-40S ribosomes while ATP hydrolysis releases Rrp5 to permit 60S assembly, and Rok1 is also required for accurate Rrp5 positioning in the nucleolus [#7, #11]. The ribosome-biogenesis role is conserved across species, supporting 47S pre-rRNA maintenance and growth in zebrafish and pre-rRNA processing with mitotic progression in Drosophila [#8, #11]. Human DDX52 acts as an ATP-dependent 3'-to-5' translocase that unwinds DNA duplexes and DNA/RNA hybrids and, conversely, possesses an annealase activity that depends on its N-terminal intrinsically disordered region and is hyperactive when helicase activity is disabled [#12]. In human cancer cells, DDX52 physically associates with c-Myc mRNA and supports c-Myc-dependent oncogenic signaling, with knockdown suppressing tumor growth [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Established that ROK1 encodes an essential DEAD-box helicase, placing it in the ATP-dependent RNA helicase class before any biochemical activity was known.\",\n      \"evidence\": \"Sequence analysis and genetic suppressor screen of the kem1 null in yeast\",\n      \"pmids\": [\"8529880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No enzymatic activity demonstrated\", \"No substrate or pathway assigned\", \"Functional link to kem1 mechanism unresolved\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Determined the subcellular distribution of Rok1, providing the first spatial context for its activity.\",\n      \"evidence\": \"Indirect immunofluorescence with affinity-purified anti-Rok1 antibodies in S. cerevisiae\",\n      \"pmids\": [\"9571634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single localization method, no functional consequence\", \"Cytoplasmic signal does not address nucleolar pool seen in later orthologs\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Showed that ATP hydrolysis is the essential catalytic core of Rok1 function, and unexpectedly that its ATPase is RNA-independent in vitro.\",\n      \"evidence\": \"In vitro ATPase assay with purified MBP-Rok1, ATPase-motif mutagenesis, and in vivo lethality tests\",\n      \"pmids\": [\"10373593\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"RNA substrate that activates ATPase in vivo not identified\", \"No structural basis for RNA-independence\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Pinpointed Rok1's specific substrate step in ribosome assembly—release of snR30—and revealed functional non-equivalence among helicase motifs.\",\n      \"evidence\": \"Quantitative snoRNA-association screen across 75 snoRNAs with motif I/III point mutants in yeast depletion strains\",\n      \"pmids\": [\"18833290\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct rRNA contact site not yet mapped\", \"Whether release is direct unwinding or remodeling unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Localized Rok1's direct pre-rRNA contacts to expansion segment ES6 in the subunit foot, providing nucleotide-resolution evidence for where it acts on snR30.\",\n      \"evidence\": \"CRAC and CLASH UV cross-linking mapping in yeast\",\n      \"pmids\": [\"24947498\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not establish catalytic order relative to Rrp5\", \"Functional consequence of each cross-link site untested\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined a nucleotide-state cycle in which ATP-bound Rok1 stabilizes Rrp5 and hydrolysis releases it, mechanistically coupling 40S remodeling to downstream 60S assembly.\",\n      \"evidence\": \"In vitro ATP/ADP-form binding assays, Rrp5 co-IP, and in vivo functional epistasis in yeast\",\n      \"pmids\": [\"27280440\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural model of the Rok1-Rrp5-pre40S complex absent\", \"Trigger for ATP hydrolysis in vivo unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated conservation of the ribosome-biogenesis role in a vertebrate, linking DDX52 to 47S pre-rRNA maintenance and organismal growth.\",\n      \"evidence\": \"Forward genetic screen, positional cloning, and 47S pre-rRNA quantification in zebrafish\",\n      \"pmids\": [\"34323273\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular step in vertebrate processing not resolved\", \"snR30 ortholog dependence not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Connected DDX52 to c-Myc oncogenic signaling, including direct binding to c-Myc mRNA, extending its biology to cancer cell proliferation.\",\n      \"evidence\": \"shRNA knockdown, RNA immunoprecipitation, xenografts, and c-Myc rescue in melanoma and prostate cancer cells\",\n      \"pmids\": [\"34233596\", \"34399732\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether c-Myc mRNA effect is via helicase activity untested\", \"Relationship to ribosome biogenesis role in tumors unclear\", \"c-Myc transcriptional feedback inferred from knockdown only\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirmed nucleolar co-localization and co-dependence of Rok1 and Rrp5 in a multicellular animal and tied Rok1 loss to mitotic arrest, reinforcing the conserved assembly mechanism.\",\n      \"evidence\": \"Drosophila mutant genetics, FISH, and developmental phenotyping\",\n      \"pmids\": [\"35628496\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mitotic defect may be indirect consequence of stalled biogenesis\", \"Direct Rrp5 interaction not biochemically shown in fly\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Resolved the human enzyme's biochemical repertoire, showing it is a 3'-5' translocase that unwinds DNA and DNA/RNA hybrids and also anneals strands via its N-terminal IDR, expanding its activity beyond canonical RNA remodeling.\",\n      \"evidence\": \"In vitro helicase/translocase and annealing assays, helicase-dead mutagenesis, and CRISPR heterozygous knockout phenotyping in U2OS cells\",\n      \"pmids\": [\"41510705\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological substrate of DNA/hybrid unwinding unknown\", \"How annealase vs helicase activity is regulated in cells unresolved\", \"Link between in vitro activities and migration/growth phenotype not established\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Implicated Rok1 in cytokinesis and chromosome segregation in fission yeast through transcriptomic effectors, broadening its phenotypic footprint.\",\n      \"evidence\": \"Live-cell imaging of actin ring and kinetochores plus RNA sequencing in S. pombe rok1 deletion\",\n      \"pmids\": [\"42016605\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Downstream effectors inferred from transcriptomics without rescue validation\", \"Direct mechanistic link to helicase activity not established\", \"May reflect indirect consequence of ribosome biogenesis defect\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DDX52's biochemically defined DNA/RNA unwinding and annealase activities relate mechanistically to its established role in pre-ribosome remodeling and to c-Myc-dependent oncogenesis remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No physiological substrate linking helicase/annealase activities to ribosome assembly\", \"No structural model of the human enzyme on substrate\", \"Mechanism connecting DDX52 to c-Myc mRNA fate undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [2, 7, 12]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 5, 10]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"GO:0140097\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [11]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3, 5, 7, 8]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [7, 8, 11]}\n    ],\n    \"complexes\": [\"pre-40S ribosome\"],\n    \"partners\": [\"RRP5\", \"snR30\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}