{"gene":"DDX27","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":2015,"finding":"DDX27 stably associates with the PeBoW-complex (Pes1, Bop1, WDR12) via an evolutionary conserved F×F motif in its N-terminal domain, and is recruited to the nucleolus via its basic C-terminal domain in an RNA-dependent manner that occurs independently of the PeBoW-complex.","method":"Mass spectrometric analysis, Co-IP, domain mapping, knockdown experiments","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with domain mutagenesis (F×F motif), mass spectrometry identification, and functional knockdown in a single rigorous study","pmids":["25825154"],"is_preprint":false},{"year":2015,"finding":"Knockdown of DDX27 (but not Pes1) causes accumulation of an extended form of the primary 47S rRNA, indicating DDX27 fulfils a critical function for proper 3' end formation of 47S rRNA independently of the PeBoW-complex.","method":"siRNA knockdown, Northern blot/rRNA analysis","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined molecular phenotype (47S rRNA processing defect), single lab, single method","pmids":["25825154"],"is_preprint":false},{"year":2018,"finding":"DDX27 regulates ribosomal RNA (rRNA) maturation and ribosome biogenesis during myogenesis, and its loss impairs skeletal muscle growth and regeneration in zebrafish.","method":"Genetic screen, zebrafish loss-of-function, rRNA maturation assays","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic screen plus in vivo loss-of-function with defined molecular (rRNA maturation) and cellular (muscle growth/regeneration) phenotypes, replicated in zebrafish model","pmids":["29518074"],"is_preprint":false},{"year":2018,"finding":"DDX27 controls the translation of specific transcripts during myogenesis, demonstrating a role in translational control of gene expression in skeletal muscle beyond general ribosome biogenesis.","method":"Ribosome profiling/translational analysis in zebrafish and cell models","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional loss-of-function with translational readout, single lab, multiple complementary methods","pmids":["29518074"],"is_preprint":false},{"year":2024,"finding":"DDX27 physically interacts with CSE1L protein, and CSE1L acts as a downstream effector of DDX27 in promoting oral squamous cell carcinoma cell growth; CSE1L depletion blocks DDX27 overexpression-induced cell proliferation.","method":"Co-immunoprecipitation, shRNA knockdown, rescue experiments, xenograft models","journal":"Life sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP plus functional rescue experiments, single lab","pmids":["38301874"],"is_preprint":false},{"year":2025,"finding":"DDX27 interacts with SRSF6 to promote alternative splicing of BRD4 pre-mRNA toward the short BRD4-S isoform, thereby activating the MAPK/ERK signaling pathway in colorectal cancer cells.","method":"Co-immunoprecipitation, RNA immunoprecipitation, splicing assays, SRSF6 phosphorylation inhibition, in vivo xenograft","journal":"Frontiers in bioscience (Landmark edition)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and RNA-IP with defined splicing and signaling phenotype, single lab, multiple orthogonal methods","pmids":["41198561"],"is_preprint":false},{"year":2025,"finding":"DDX27 knockdown reduces EZH2 protein levels and significantly lowers EZH2 promoter luciferase activity, indicating that DDX27 promotes colorectal cancer progression partly through transcriptional upregulation of EZH2.","method":"siRNA knockdown, luciferase reporter assay, RNA-seq, Western blot, in vivo xenograft","journal":"Pathology, research and practice","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter assay plus RNA-seq and in vivo validation, single lab, multiple orthogonal methods","pmids":["41045764"],"is_preprint":false}],"current_model":"DDX27 is a nucleolar DEAD-box RNA helicase that stably associates with the PeBoW-complex via an N-terminal F×F motif to promote 3' end processing of 47S pre-rRNA and ribosome biogenesis; it also regulates alternative pre-mRNA splicing (promoting BRD4-S production via SRSF6 interaction) and transcriptional upregulation of EZH2, collectively linking ribosome biogenesis and RNA processing functions to skeletal muscle growth, regeneration, and cancer progression."},"narrative":{"mechanistic_narrative":"DDX27 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis through its association with the rRNA processing machinery [PMID:25825154, PMID:29518074]. It stably binds the PeBoW-complex (Pes1, Bop1, WDR12) via a conserved F×F motif in its N-terminal domain, while its basic C-terminal domain mediates RNA-dependent recruitment to the nucleolus independently of PeBoW [PMID:25825154]. DDX27 is required for proper 3' end formation of the primary 47S pre-rRNA, a function it carries out independently of the PeBoW-complex, since its loss causes accumulation of an extended 47S species [PMID:25825154]. Through control of rRNA maturation and ribosome biogenesis, DDX27 governs the translation of specific transcripts during myogenesis, and its loss impairs skeletal muscle growth and regeneration in vivo [PMID:29518074]. Beyond ribosome biogenesis, DDX27 participates in cancer-associated RNA processing and gene regulation: it interacts with SRSF6 to direct alternative splicing of BRD4 pre-mRNA toward the BRD4-S isoform and activate MAPK/ERK signaling [PMID:41198561], promotes oral squamous carcinoma growth through the downstream effector CSE1L [PMID:38301874], and drives colorectal cancer progression in part by transcriptional upregulation of EZH2 [PMID:41045764].","teleology":[{"year":2015,"claim":"Established how DDX27 is anchored within the nucleolar ribosome biogenesis machinery, defining the molecular basis of its recruitment and its complex membership.","evidence":"Mass spectrometry, reciprocal Co-IP, and domain mapping with F×F motif mutagenesis in human cells","pmids":["25825154"],"confidence":"High","gaps":["Helicase catalytic activity on rRNA not directly demonstrated","Functional consequence of PeBoW association versus independent nucleolar recruitment not separated"]},{"year":2015,"claim":"Assigned DDX27 a specific, PeBoW-independent step in pre-rRNA processing by showing it is required for correct 47S 3' end formation.","evidence":"siRNA knockdown of DDX27 versus Pes1 with Northern/rRNA processing analysis","pmids":["25825154"],"confidence":"Medium","gaps":["Direct enzymatic mechanism of 3' end maturation not resolved","Single method (rRNA analysis) from one lab"]},{"year":2018,"claim":"Connected DDX27's rRNA maturation function to an in vivo physiological process, showing ribosome biogenesis through DDX27 is required for skeletal muscle growth and regeneration.","evidence":"Genetic screen and zebrafish loss-of-function with rRNA maturation and translational profiling readouts","pmids":["29518074"],"confidence":"High","gaps":["Mechanism linking specific transcript translation to muscle phenotype not fully defined","Direct rRNA substrate engagement not shown in vivo"]},{"year":2024,"claim":"Extended DDX27 function to tumor growth by identifying CSE1L as a physical partner and required downstream effector in oral squamous cell carcinoma.","evidence":"Co-IP, shRNA knockdown, rescue experiments, and xenograft models","pmids":["38301874"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation","Mechanism by which DDX27 controls CSE1L unknown"]},{"year":2025,"claim":"Defined a splicing-regulatory role for DDX27, showing it cooperates with SRSF6 to bias BRD4 splicing toward BRD4-S and activate MAPK/ERK signaling in colorectal cancer.","evidence":"Co-IP, RNA-IP, splicing assays, SRSF6 phosphorylation inhibition, and xenograft","pmids":["41198561"],"confidence":"Medium","gaps":["Direct binding of DDX27 to BRD4 pre-mRNA versus indirect via SRSF6 not fully separated","Single lab"]},{"year":2025,"claim":"Implicated DDX27 in transcriptional control by linking it to upregulation of EZH2 during colorectal cancer progression.","evidence":"siRNA knockdown, EZH2 promoter luciferase reporter, RNA-seq, Western blot, and xenograft","pmids":["41045764"],"confidence":"Medium","gaps":["Mechanism by which a nucleolar helicase affects EZH2 promoter activity unresolved","Direct versus indirect transcriptional effect not distinguished"]},{"year":null,"claim":"Whether DDX27's nucleolar rRNA-processing activity mechanistically underlies its disparate cancer-associated splicing, transcriptional, and protein-partner functions remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying mechanism connecting ribosome biogenesis to splicing/transcriptional roles","Direct RNA helicase activity not biochemically reconstituted","Substrate specificity of the helicase domain uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,5]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[1,2]}],"localization":[{"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":[1,2]}],"complexes":["PeBoW complex"],"partners":["PES1","BOP1","WDR12","SRSF6","CSE1L"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96GQ7","full_name":"Probable ATP-dependent RNA helicase DDX27","aliases":["DEAD box protein 27"],"length_aa":765,"mass_kda":86.6,"function":"Probable ATP-dependent RNA helicase. Component of the nucleolar ribosomal RNA (rRNA) processing machinery that regulates 3' end formation of ribosomal 47S rRNA (PubMed:25825154)","subcellular_location":"Nucleus, nucleolus; Chromosome","url":"https://www.uniprot.org/uniprotkb/Q96GQ7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DDX27","classification":"Common Essential","n_dependent_lines":1174,"n_total_lines":1208,"dependency_fraction":0.9718543046357616},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"WDR12","stoichiometry":4.0},{"gene":"HSF1","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DDX27","total_profiled":1310},"omim":[{"mim_id":"616621","title":"DEAD-BOX HELICASE 27; DDX27","url":"https://www.omim.org/entry/616621"},{"mim_id":"616620","title":"WD REPEAT-CONTAINING PROTEIN 12; WDR12","url":"https://www.omim.org/entry/616620"},{"mim_id":"610596","title":"BLOCK OF PROLIFERATION 1; BOP1","url":"https://www.omim.org/entry/610596"},{"mim_id":"605819","title":"PESCADILLO RIBOSOMAL BIOGENESIS FACTOR 1; PES1","url":"https://www.omim.org/entry/605819"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DDX27"},"hgnc":{"alias_symbol":["dJ686N3.1","DRS1"],"prev_symbol":[]},"alphafold":{"accession":"Q96GQ7","domains":[{"cath_id":"3.40.50.300","chopping":"210-425","consensus_level":"high","plddt":87.8259,"start":210,"end":425},{"cath_id":"3.40.50.300","chopping":"436-606","consensus_level":"high","plddt":87.6608,"start":436,"end":606}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GQ7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GQ7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GQ7-F1-predicted_aligned_error_v6.png","plddt_mean":72.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DDX27","jax_strain_url":"https://www.jax.org/strain/search?query=DDX27"},"sequence":{"accession":"Q96GQ7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96GQ7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96GQ7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GQ7"}},"corpus_meta":[{"pmid":"29518074","id":"PMC_29518074","title":"RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes.","date":"2018","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29518074","citation_count":39,"is_preprint":false},{"pmid":"25825154","id":"PMC_25825154","title":"DEAD-box helicase DDX27 regulates 3' end formation of ribosomal 47S RNA and stably associates with the PeBoW-complex.","date":"2015","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/25825154","citation_count":36,"is_preprint":false},{"pmid":"37370759","id":"PMC_37370759","title":"METTL3-Modulated circUHRF2 Promotes Colorectal Cancer Stemness and Metastasis through Increasing DDX27 mRNA Stability by Recruiting IGF2BP1.","date":"2023","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/37370759","citation_count":23,"is_preprint":false},{"pmid":"38939334","id":"PMC_38939334","title":"miR-617 interacts with the promoter of DDX27 and positively regulates its expression: implications for cancer therapeutics.","date":"2024","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38939334","citation_count":9,"is_preprint":false},{"pmid":"38301874","id":"PMC_38301874","title":"DDX27 regulates oral squamous cell carcinoma development through targeting CSE1L.","date":"2024","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38301874","citation_count":8,"is_preprint":false},{"pmid":"36551703","id":"PMC_36551703","title":"Circ_RNF13 Regulates the Stemness and Chemosensitivity of Colorectal Cancer by Transcriptional Regulation of DDX27 Mediated by TRIM24 Stabilization.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36551703","citation_count":8,"is_preprint":false},{"pmid":"40394785","id":"PMC_40394785","title":"DDX27: An RNA helicase regulating cancer progression and therapeutic prospects.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40394785","citation_count":4,"is_preprint":false},{"pmid":"40877927","id":"PMC_40877927","title":"DDX27 in cancer: molecular mechanisms, clinical implications, and therapeutic potential.","date":"2025","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40877927","citation_count":1,"is_preprint":false},{"pmid":"41045764","id":"PMC_41045764","title":"DNA methylation-regulated DDX27 promotes colorectal cancer progression through EZH2.","date":"2025","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/41045764","citation_count":0,"is_preprint":false},{"pmid":"41198561","id":"PMC_41198561","title":"BRD4-S Drives Colorectal Cancer Progression via DDX27-Regulated Splicing and MAPK Signaling Activation.","date":"2025","source":"Frontiers in bioscience (Landmark edition)","url":"https://pubmed.ncbi.nlm.nih.gov/41198561","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.15.25327674","title":"Genome-wide association studies of social participation and occupational engagement in the UK Biobank","date":"2025-05-15","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.15.25327674","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8193,"output_tokens":1507,"usd":0.023592,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8284,"output_tokens":2375,"usd":0.050397,"stage2_stop_reason":"end_turn"},"total_usd":0.073989,"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\": 2015,\n      \"finding\": \"DDX27 stably associates with the PeBoW-complex (Pes1, Bop1, WDR12) via an evolutionary conserved F×F motif in its N-terminal domain, and is recruited to the nucleolus via its basic C-terminal domain in an RNA-dependent manner that occurs independently of the PeBoW-complex.\",\n      \"method\": \"Mass spectrometric analysis, Co-IP, domain mapping, knockdown experiments\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with domain mutagenesis (F×F motif), mass spectrometry identification, and functional knockdown in a single rigorous study\",\n      \"pmids\": [\"25825154\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Knockdown of DDX27 (but not Pes1) causes accumulation of an extended form of the primary 47S rRNA, indicating DDX27 fulfils a critical function for proper 3' end formation of 47S rRNA independently of the PeBoW-complex.\",\n      \"method\": \"siRNA knockdown, Northern blot/rRNA analysis\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined molecular phenotype (47S rRNA processing defect), single lab, single method\",\n      \"pmids\": [\"25825154\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DDX27 regulates ribosomal RNA (rRNA) maturation and ribosome biogenesis during myogenesis, and its loss impairs skeletal muscle growth and regeneration in zebrafish.\",\n      \"method\": \"Genetic screen, zebrafish loss-of-function, rRNA maturation assays\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic screen plus in vivo loss-of-function with defined molecular (rRNA maturation) and cellular (muscle growth/regeneration) phenotypes, replicated in zebrafish model\",\n      \"pmids\": [\"29518074\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DDX27 controls the translation of specific transcripts during myogenesis, demonstrating a role in translational control of gene expression in skeletal muscle beyond general ribosome biogenesis.\",\n      \"method\": \"Ribosome profiling/translational analysis in zebrafish and cell models\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional loss-of-function with translational readout, single lab, multiple complementary methods\",\n      \"pmids\": [\"29518074\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DDX27 physically interacts with CSE1L protein, and CSE1L acts as a downstream effector of DDX27 in promoting oral squamous cell carcinoma cell growth; CSE1L depletion blocks DDX27 overexpression-induced cell proliferation.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown, rescue experiments, xenograft models\",\n      \"journal\": \"Life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP plus functional rescue experiments, single lab\",\n      \"pmids\": [\"38301874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX27 interacts with SRSF6 to promote alternative splicing of BRD4 pre-mRNA toward the short BRD4-S isoform, thereby activating the MAPK/ERK signaling pathway in colorectal cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, RNA immunoprecipitation, splicing assays, SRSF6 phosphorylation inhibition, in vivo xenograft\",\n      \"journal\": \"Frontiers in bioscience (Landmark edition)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and RNA-IP with defined splicing and signaling phenotype, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41198561\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX27 knockdown reduces EZH2 protein levels and significantly lowers EZH2 promoter luciferase activity, indicating that DDX27 promotes colorectal cancer progression partly through transcriptional upregulation of EZH2.\",\n      \"method\": \"siRNA knockdown, luciferase reporter assay, RNA-seq, Western blot, in vivo xenograft\",\n      \"journal\": \"Pathology, research and practice\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter assay plus RNA-seq and in vivo validation, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41045764\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DDX27 is a nucleolar DEAD-box RNA helicase that stably associates with the PeBoW-complex via an N-terminal F×F motif to promote 3' end processing of 47S pre-rRNA and ribosome biogenesis; it also regulates alternative pre-mRNA splicing (promoting BRD4-S production via SRSF6 interaction) and transcriptional upregulation of EZH2, collectively linking ribosome biogenesis and RNA processing functions to skeletal muscle growth, regeneration, and cancer progression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DDX27 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis through its association with the rRNA processing machinery [#0, #2]. It stably binds the PeBoW-complex (Pes1, Bop1, WDR12) via a conserved F\\u00d7F motif in its N-terminal domain, while its basic C-terminal domain mediates RNA-dependent recruitment to the nucleolus independently of PeBoW [#0]. DDX27 is required for proper 3' end formation of the primary 47S pre-rRNA, a function it carries out independently of the PeBoW-complex, since its loss causes accumulation of an extended 47S species [#1]. Through control of rRNA maturation and ribosome biogenesis, DDX27 governs the translation of specific transcripts during myogenesis, and its loss impairs skeletal muscle growth and regeneration in vivo [#2, #3]. Beyond ribosome biogenesis, DDX27 participates in cancer-associated RNA processing and gene regulation: it interacts with SRSF6 to direct alternative splicing of BRD4 pre-mRNA toward the BRD4-S isoform and activate MAPK/ERK signaling [#5], promotes oral squamous carcinoma growth through the downstream effector CSE1L [#4], and drives colorectal cancer progression in part by transcriptional upregulation of EZH2 [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Established how DDX27 is anchored within the nucleolar ribosome biogenesis machinery, defining the molecular basis of its recruitment and its complex membership.\",\n      \"evidence\": \"Mass spectrometry, reciprocal Co-IP, and domain mapping with F\\u00d7F motif mutagenesis in human cells\",\n      \"pmids\": [\n        \"25825154\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Helicase catalytic activity on rRNA not directly demonstrated\",\n        \"Functional consequence of PeBoW association versus independent nucleolar recruitment not separated\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Assigned DDX27 a specific, PeBoW-independent step in pre-rRNA processing by showing it is required for correct 47S 3' end formation.\",\n      \"evidence\": \"siRNA knockdown of DDX27 versus Pes1 with Northern/rRNA processing analysis\",\n      \"pmids\": [\n        \"25825154\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct enzymatic mechanism of 3' end maturation not resolved\",\n        \"Single method (rRNA analysis) from one lab\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected DDX27's rRNA maturation function to an in vivo physiological process, showing ribosome biogenesis through DDX27 is required for skeletal muscle growth and regeneration.\",\n      \"evidence\": \"Genetic screen and zebrafish loss-of-function with rRNA maturation and translational profiling readouts\",\n      \"pmids\": [\n        \"29518074\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism linking specific transcript translation to muscle phenotype not fully defined\",\n        \"Direct rRNA substrate engagement not shown in vivo\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended DDX27 function to tumor growth by identifying CSE1L as a physical partner and required downstream effector in oral squamous cell carcinoma.\",\n      \"evidence\": \"Co-IP, shRNA knockdown, rescue experiments, and xenograft models\",\n      \"pmids\": [\n        \"38301874\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation\",\n        \"Mechanism by which DDX27 controls CSE1L unknown\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a splicing-regulatory role for DDX27, showing it cooperates with SRSF6 to bias BRD4 splicing toward BRD4-S and activate MAPK/ERK signaling in colorectal cancer.\",\n      \"evidence\": \"Co-IP, RNA-IP, splicing assays, SRSF6 phosphorylation inhibition, and xenograft\",\n      \"pmids\": [\n        \"41198561\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct binding of DDX27 to BRD4 pre-mRNA versus indirect via SRSF6 not fully separated\",\n        \"Single lab\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated DDX27 in transcriptional control by linking it to upregulation of EZH2 during colorectal cancer progression.\",\n      \"evidence\": \"siRNA knockdown, EZH2 promoter luciferase reporter, RNA-seq, Western blot, and xenograft\",\n      \"pmids\": [\n        \"41045764\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which a nucleolar helicase affects EZH2 promoter activity unresolved\",\n        \"Direct versus indirect transcriptional effect not distinguished\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether DDX27's nucleolar rRNA-processing activity mechanistically underlies its disparate cancer-associated splicing, transcriptional, and protein-partner functions remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unifying mechanism connecting ribosome biogenesis to splicing/transcriptional roles\",\n        \"Direct RNA helicase activity not biochemically reconstituted\",\n        \"Substrate specificity of the helicase domain uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0003723\",\n        \"supporting_discovery_ids\": [\n          0,\n          5\n        ]\n      },\n      {\n        \"term_id\": \"GO:0140098\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005730\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-8953854\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"PeBoW complex\"\n    ],\n    \"partners\": [\n      \"PES1\",\n      \"BOP1\",\n      \"WDR12\",\n      \"SRSF6\",\n      \"CSE1L\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}