{"gene":"UTP11","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2023,"finding":"UTP11 binds to the pre-rRNA processing factor MPP10 and plays an important role in the biosynthesis of 18S ribosomal RNA (rRNA). Depletion of UTP11 impedes 18S rRNA biosynthesis, triggering nucleolar stress that prevents MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins RPL5 and RPL11.","method":"Co-immunoprecipitation (binding to MPP10), rRNA processing assays, in vitro/in vivo knockdown with p53/MDM2/RPL5/RPL11 pathway analysis","journal":"Redox biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (binding assay, rRNA biosynthesis assay, epistasis via RPL5/RPL11/MDM2/p53), in vitro and in vivo validation, single lab but mechanistically rigorous","pmids":["37087976"],"is_preprint":false},{"year":2023,"finding":"UTP11 deficiency represses expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced glutathione (GSH) levels and enhanced ferroptosis, representing a p53-independent mechanism by which UTP11 loss suppresses cancer cell survival.","method":"Knockdown experiments with SLC7A11/NRF2 mRNA stability assays (Actinomycin D chase), GSH measurement, ferroptosis assays in vitro and in vivo","journal":"Redox biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (mRNA stability, GSH quantification, ferroptosis readout), in vitro and in vivo, same rigorous study","pmids":["37087976"],"is_preprint":false},{"year":2002,"finding":"CGI-94 (UTP11) contains a bipartite nuclear localization signal and, when expressed as a GFP fusion protein, is translocated into the nucleus; the protein is also observed in the cytoplasm and extracellular space, indicating it can traffic between compartments.","method":"GFP-fusion transfection and fluorescence microscopy for subcellular localization","journal":"The European journal of neuroscience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single imaging method, no functional consequence directly linked to localization","pmids":["11860508"],"is_preprint":false},{"year":2003,"finding":"CGI-94 (UTP11) physically interacts with SMAC/Diablo (second mitochondria-derived activator of caspases), and neuronal overexpression of CGI-94 inhibits NGF-induced neurite outgrowth and leads to cell death, implicating it in regulation of neuronal apoptosis.","method":"Protein-protein interaction assay (co-immunoprecipitation/pulldown with SMAC/Diablo), neurite outgrowth assay, cell viability assay upon overexpression","journal":"Neuroscience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single pulldown method for interaction, limited mechanistic follow-up","pmids":["12559088"],"is_preprint":false},{"year":2024,"finding":"UTP11 knockdown in hepatocellular carcinoma cells reduces the mRNA stability of Oct4 (a stemness factor), as measured by Actinomycin D chase assays, linking UTP11 to mRNA stabilization of stem cell-related transcripts.","method":"Actinomycin D mRNA stability assay, qRT-PCR, knockdown experiments, in vivo xenograft","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct mRNA stability assay with functional knockdown, single lab, no mechanistic dissection of how UTP11 stabilizes Oct4 mRNA","pmids":["38233795"],"is_preprint":false}],"current_model":"UTP11 is a nucleolar protein that supports 18S rRNA biogenesis by binding the pre-rRNA processing factor MPP10; its loss triggers nucleolar/ribosomal stress that stabilizes p53 (via RPL5/RPL11-mediated inhibition of MDM2) and independently promotes ferroptosis by destabilizing NRF2 mRNA to suppress SLC7A11 and glutathione levels, while it also stabilizes mRNAs such as Oct4 in cancer cells; an earlier study identified an interaction with the pro-apoptotic protein SMAC/Diablo and a nuclear localization signal, suggesting additional roles in apoptosis regulation."},"narrative":{"mechanistic_narrative":"UTP11 is a nucleolar pre-rRNA processing factor required for 18S ribosomal RNA biogenesis, where it acts through physical association with the processing factor MPP10 [PMID:37087976]. Its depletion impedes 18S rRNA biosynthesis and triggers nucleolar stress, which prevents MDM2-mediated ubiquitination and degradation of p53 via the ribosomal proteins RPL5 and RPL11, thereby stabilizing p53 [PMID:37087976]. Independently of p53, loss of UTP11 promotes the decay of NRF2 mRNA, repressing SLC7A11 expression and lowering glutathione levels to sensitize cancer cells to ferroptosis [PMID:37087976]. Beyond ribosome biogenesis, UTP11 also functions in mRNA stabilization, supporting the stability of the stemness transcript Oct4 in hepatocellular carcinoma cells [PMID:38233795]. Earlier work links the protein to nuclear-cytoplasmic trafficking via a bipartite nuclear localization signal [PMID:11860508] and to neuronal apoptosis through interaction with SMAC/Diablo [PMID:12559088], but these roles are not mechanistically integrated with its rRNA function in the available corpus.","teleology":[{"year":2002,"claim":"The first question was where UTP11 (then CGI-94) resides in the cell; identifying a nuclear localization signal established it as a compartment-trafficking protein capable of nuclear entry.","evidence":"GFP-fusion transfection and fluorescence microscopy","pmids":["11860508"],"confidence":"Low","gaps":["Single imaging method with no functional consequence tied to localization","Did not connect nuclear localization to any molecular activity","Cytoplasmic and extracellular signals not mechanistically explained"]},{"year":2003,"claim":"An early attempt to assign function tested whether UTP11 participates in apoptosis, finding a physical interaction with SMAC/Diablo and an anti-neuritogenic, pro-death effect on neurons.","evidence":"Co-immunoprecipitation/pulldown with SMAC/Diablo, neurite outgrowth and viability assays upon overexpression","pmids":["12559088"],"confidence":"Low","gaps":["Single pulldown without reciprocal validation","Overexpression phenotype may not reflect endogenous function","Apoptotic role never reconciled with later rRNA biogenesis function"]},{"year":2023,"claim":"The defining mechanistic advance established UTP11 as an MPP10-associated factor essential for 18S rRNA biogenesis and showed that its loss couples nucleolar stress to RPL5/RPL11-dependent p53 stabilization.","evidence":"Co-IP with MPP10, rRNA processing assays, and knockdown epistasis through the RPL5/RPL11/MDM2/p53 axis in vitro and in vivo","pmids":["37087976"],"confidence":"High","gaps":["Structural basis of the UTP11-MPP10 interaction not resolved","Position of UTP11 within the small-subunit processome not defined","Catalytic versus scaffolding contribution to processing unclear"]},{"year":2023,"claim":"The same study resolved whether UTP11 loss kills cells only through p53, demonstrating a parallel ferroptosis pathway in which UTP11 deficiency destabilizes NRF2 mRNA to suppress SLC7A11 and glutathione.","evidence":"NRF2/SLC7A11 mRNA stability (Actinomycin D chase), GSH quantification, and ferroptosis assays in vitro and in vivo","pmids":["37087976"],"confidence":"High","gaps":["How UTP11 controls NRF2 mRNA stability mechanistically is undefined","Whether direct RNA binding mediates the effect is unknown","Link between rRNA biogenesis role and mRNA decay control unestablished"]},{"year":2024,"claim":"A subsequent study extended UTP11's RNA-stabilizing role beyond NRF2 by showing it supports Oct4 mRNA stability in hepatocellular carcinoma, connecting it to cancer stemness.","evidence":"Actinomycin D mRNA stability assay, qRT-PCR, knockdown, and xenograft","pmids":["38233795"],"confidence":"Medium","gaps":["Mechanism by which UTP11 stabilizes Oct4 mRNA not dissected","No demonstration of direct UTP11-Oct4 mRNA binding","Single lab without independent replication"]},{"year":null,"claim":"It remains unknown how UTP11's core role in 18S rRNA processing relates mechanistically to its apparent control of specific mRNA stability (NRF2, Oct4) and to its earlier reported apoptotic interactions.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of UTP11 in the processome","Whether UTP11 binds mRNA directly is undetermined","The SMAC/Diablo apoptotic role is not integrated with ribosome biogenesis function"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[1]}],"complexes":[],"partners":["MPP10","SMAC/DIABLO"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y3A2","full_name":"Probable U3 small nucleolar RNA-associated protein 11","aliases":["UTP11-like protein"],"length_aa":253,"mass_kda":30.4,"function":"Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9Y3A2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/UTP11","classification":"Common Essential","n_dependent_lines":1136,"n_total_lines":1208,"dependency_fraction":0.9403973509933775},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/UTP11","total_profiled":1310},"omim":[{"mim_id":"609440","title":"UTP11-LIKE PROTEIN; UTP11L","url":"https://www.omim.org/entry/609440"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoli","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":111.8},{"tissue":"tongue","ntpm":79.8}],"url":"https://www.proteinatlas.org/search/UTP11"},"hgnc":{"alias_symbol":["CGI-94"],"prev_symbol":["UTP11L"]},"alphafold":{"accession":"Q9Y3A2","domains":[{"cath_id":"-","chopping":"133-205","consensus_level":"medium","plddt":90.1616,"start":133,"end":205},{"cath_id":"1.20.5","chopping":"93-123","consensus_level":"medium","plddt":95.2629,"start":93,"end":123}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3A2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3A2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3A2-F1-predicted_aligned_error_v6.png","plddt_mean":91.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=UTP11","jax_strain_url":"https://www.jax.org/strain/search?query=UTP11"},"sequence":{"accession":"Q9Y3A2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y3A2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y3A2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3A2"}},"corpus_meta":[{"pmid":"23267699","id":"PMC_23267699","title":"Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells.","date":"2012","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/23267699","citation_count":44,"is_preprint":false},{"pmid":"37087976","id":"PMC_37087976","title":"UTP11 deficiency suppresses cancer development via nucleolar stress and ferroptosis.","date":"2023","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/37087976","citation_count":21,"is_preprint":false},{"pmid":"11860508","id":"PMC_11860508","title":"Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain.","date":"2002","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/11860508","citation_count":11,"is_preprint":false},{"pmid":"30372444","id":"PMC_30372444","title":"Mouse genome-wide association studies and systems genetics uncover the genetic architecture associated with hepatic pharmacokinetic and pharmacodynamic properties of a constrained ethyl antisense oligonucleotide targeting Malat1.","date":"2018","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30372444","citation_count":7,"is_preprint":false},{"pmid":"39800194","id":"PMC_39800194","title":"VAMP8 as a biomarker and potential therapeutic target for endothelial cell dysfunction in atherosclerosis.","date":"2025","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/39800194","citation_count":5,"is_preprint":false},{"pmid":"39537071","id":"PMC_39537071","title":"The landscape of intrinsically disordered proteins in Leishmania parasite: Implications for drug discovery.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39537071","citation_count":2,"is_preprint":false},{"pmid":"35625741","id":"PMC_35625741","title":"Whole-Exome Sequencing of Germline Variants in Non-BRCA Families with Hereditary Breast Cancer.","date":"2022","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/35625741","citation_count":2,"is_preprint":false},{"pmid":"38233795","id":"PMC_38233795","title":"UTP11 promotes the growth of hepatocellular carcinoma by enhancing the mRNA stability of Oct4.","date":"2024","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38233795","citation_count":1,"is_preprint":false},{"pmid":"40045424","id":"PMC_40045424","title":"Mendelian randomization provides a multi-omics perspective on the regulation of genes involved in ribosome biogenesis in relation to cardiac structure and function.","date":"2025","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/40045424","citation_count":1,"is_preprint":false},{"pmid":"12559088","id":"PMC_12559088","title":"Comparative gene identification-94--a pivotal regulator of apoptosis.","date":"2003","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/12559088","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7836,"output_tokens":1316,"usd":0.021624,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7975,"output_tokens":2135,"usd":0.046625,"stage2_stop_reason":"end_turn"},"total_usd":0.068249,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"UTP11 binds to the pre-rRNA processing factor MPP10 and plays an important role in the biosynthesis of 18S ribosomal RNA (rRNA). Depletion of UTP11 impedes 18S rRNA biosynthesis, triggering nucleolar stress that prevents MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins RPL5 and RPL11.\",\n      \"method\": \"Co-immunoprecipitation (binding to MPP10), rRNA processing assays, in vitro/in vivo knockdown with p53/MDM2/RPL5/RPL11 pathway analysis\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (binding assay, rRNA biosynthesis assay, epistasis via RPL5/RPL11/MDM2/p53), in vitro and in vivo validation, single lab but mechanistically rigorous\",\n      \"pmids\": [\"37087976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"UTP11 deficiency represses expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced glutathione (GSH) levels and enhanced ferroptosis, representing a p53-independent mechanism by which UTP11 loss suppresses cancer cell survival.\",\n      \"method\": \"Knockdown experiments with SLC7A11/NRF2 mRNA stability assays (Actinomycin D chase), GSH measurement, ferroptosis assays in vitro and in vivo\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (mRNA stability, GSH quantification, ferroptosis readout), in vitro and in vivo, same rigorous study\",\n      \"pmids\": [\"37087976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"CGI-94 (UTP11) contains a bipartite nuclear localization signal and, when expressed as a GFP fusion protein, is translocated into the nucleus; the protein is also observed in the cytoplasm and extracellular space, indicating it can traffic between compartments.\",\n      \"method\": \"GFP-fusion transfection and fluorescence microscopy for subcellular localization\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single imaging method, no functional consequence directly linked to localization\",\n      \"pmids\": [\"11860508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"CGI-94 (UTP11) physically interacts with SMAC/Diablo (second mitochondria-derived activator of caspases), and neuronal overexpression of CGI-94 inhibits NGF-induced neurite outgrowth and leads to cell death, implicating it in regulation of neuronal apoptosis.\",\n      \"method\": \"Protein-protein interaction assay (co-immunoprecipitation/pulldown with SMAC/Diablo), neurite outgrowth assay, cell viability assay upon overexpression\",\n      \"journal\": \"Neuroscience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pulldown method for interaction, limited mechanistic follow-up\",\n      \"pmids\": [\"12559088\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"UTP11 knockdown in hepatocellular carcinoma cells reduces the mRNA stability of Oct4 (a stemness factor), as measured by Actinomycin D chase assays, linking UTP11 to mRNA stabilization of stem cell-related transcripts.\",\n      \"method\": \"Actinomycin D mRNA stability assay, qRT-PCR, knockdown experiments, in vivo xenograft\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct mRNA stability assay with functional knockdown, single lab, no mechanistic dissection of how UTP11 stabilizes Oct4 mRNA\",\n      \"pmids\": [\"38233795\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"UTP11 is a nucleolar protein that supports 18S rRNA biogenesis by binding the pre-rRNA processing factor MPP10; its loss triggers nucleolar/ribosomal stress that stabilizes p53 (via RPL5/RPL11-mediated inhibition of MDM2) and independently promotes ferroptosis by destabilizing NRF2 mRNA to suppress SLC7A11 and glutathione levels, while it also stabilizes mRNAs such as Oct4 in cancer cells; an earlier study identified an interaction with the pro-apoptotic protein SMAC/Diablo and a nuclear localization signal, suggesting additional roles in apoptosis regulation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"UTP11 is a nucleolar pre-rRNA processing factor required for 18S ribosomal RNA biogenesis, where it acts through physical association with the processing factor MPP10 [#0]. Its depletion impedes 18S rRNA biosynthesis and triggers nucleolar stress, which prevents MDM2-mediated ubiquitination and degradation of p53 via the ribosomal proteins RPL5 and RPL11, thereby stabilizing p53 [#0]. Independently of p53, loss of UTP11 promotes the decay of NRF2 mRNA, repressing SLC7A11 expression and lowering glutathione levels to sensitize cancer cells to ferroptosis [#1]. Beyond ribosome biogenesis, UTP11 also functions in mRNA stabilization, supporting the stability of the stemness transcript Oct4 in hepatocellular carcinoma cells [#4]. Earlier work links the protein to nuclear-cytoplasmic trafficking via a bipartite nuclear localization signal [#2] and to neuronal apoptosis through interaction with SMAC/Diablo [#3], but these roles are not mechanistically integrated with its rRNA function in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"The first question was where UTP11 (then CGI-94) resides in the cell; identifying a nuclear localization signal established it as a compartment-trafficking protein capable of nuclear entry.\",\n      \"evidence\": \"GFP-fusion transfection and fluorescence microscopy\",\n      \"pmids\": [\"11860508\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single imaging method with no functional consequence tied to localization\", \"Did not connect nuclear localization to any molecular activity\", \"Cytoplasmic and extracellular signals not mechanistically explained\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"An early attempt to assign function tested whether UTP11 participates in apoptosis, finding a physical interaction with SMAC/Diablo and an anti-neuritogenic, pro-death effect on neurons.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown with SMAC/Diablo, neurite outgrowth and viability assays upon overexpression\",\n      \"pmids\": [\"12559088\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single pulldown without reciprocal validation\", \"Overexpression phenotype may not reflect endogenous function\", \"Apoptotic role never reconciled with later rRNA biogenesis function\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The defining mechanistic advance established UTP11 as an MPP10-associated factor essential for 18S rRNA biogenesis and showed that its loss couples nucleolar stress to RPL5/RPL11-dependent p53 stabilization.\",\n      \"evidence\": \"Co-IP with MPP10, rRNA processing assays, and knockdown epistasis through the RPL5/RPL11/MDM2/p53 axis in vitro and in vivo\",\n      \"pmids\": [\"37087976\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the UTP11-MPP10 interaction not resolved\", \"Position of UTP11 within the small-subunit processome not defined\", \"Catalytic versus scaffolding contribution to processing unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The same study resolved whether UTP11 loss kills cells only through p53, demonstrating a parallel ferroptosis pathway in which UTP11 deficiency destabilizes NRF2 mRNA to suppress SLC7A11 and glutathione.\",\n      \"evidence\": \"NRF2/SLC7A11 mRNA stability (Actinomycin D chase), GSH quantification, and ferroptosis assays in vitro and in vivo\",\n      \"pmids\": [\"37087976\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How UTP11 controls NRF2 mRNA stability mechanistically is undefined\", \"Whether direct RNA binding mediates the effect is unknown\", \"Link between rRNA biogenesis role and mRNA decay control unestablished\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A subsequent study extended UTP11's RNA-stabilizing role beyond NRF2 by showing it supports Oct4 mRNA stability in hepatocellular carcinoma, connecting it to cancer stemness.\",\n      \"evidence\": \"Actinomycin D mRNA stability assay, qRT-PCR, knockdown, and xenograft\",\n      \"pmids\": [\"38233795\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which UTP11 stabilizes Oct4 mRNA not dissected\", \"No demonstration of direct UTP11-Oct4 mRNA binding\", \"Single lab without independent replication\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how UTP11's core role in 18S rRNA processing relates mechanistically to its apparent control of specific mRNA stability (NRF2, Oct4) and to its earlier reported apoptotic interactions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of UTP11 in the processome\", \"Whether UTP11 binds mRNA directly is undetermined\", \"The SMAC/Diablo apoptotic role is not integrated with ribosome biogenesis function\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MPP10\", \"SMAC/DIABLO\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":5,"faith_total":5,"faith_pct":100.0}}