{"gene":"TAF1D","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2007,"finding":"TAF1D (then called TAF(I)41 / MGC5306) was identified as a novel subunit of the RNA polymerase I transcription factor SL1. It co-purifies and co-immunoprecipitates with SL1, resides at the rDNA promoter in the nucleolus, and is required for Pol I transcription: immunodepletion of TAF(I)41 from nuclear extracts drastically reduces Pol I transcription (rescued by adding recombinant SL1), and siRNA-mediated knockdown in cells causes loss of SL1 from the rDNA promoter, displacement of Pol I from the rDNA, and reduced pre-rRNA synthesis.","method":"Co-purification, reciprocal co-immunoprecipitation, immunodepletion/reconstitution in vitro transcription assay, siRNA knockdown with ChIP and pre-rRNA synthesis readout","journal":"The EMBO Journal","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (biochemical purification, reciprocal Co-IP, immunodepletion/reconstitution, siRNA + ChIP) in a single rigorous study","pmids":["17318177"],"is_preprint":false},{"year":2004,"finding":"TAF1D (MGC5306) was identified as a nuclear protein that interacts with DNA polymerase beta (polβ), including both wild-type polβ and a truncated cancer-associated form (polβΔ), as demonstrated by yeast two-hybrid screening and confirmed by co-immunoprecipitation/Western blot. TAF1D localizes to the nucleus (shown by GFP fusion), is expressed in human carcinomas and tumor cell lines but not normal tissues, and siRNA-mediated knockdown produces anti-growth effects and modulation of cell-cycle events.","method":"Yeast two-hybrid screen, co-immunoprecipitation/Western blot, GFP-fusion nuclear localization, siRNA knockdown with cell-cycle analysis","journal":"Cancer Research","confidence":"Medium","confidence_rationale":"Tier 2–3 — Y2H confirmed by Co-IP and localization, but single lab and limited mechanistic follow-up on polβ interaction function","pmids":["15520167"],"is_preprint":false},{"year":2023,"finding":"In MYCN-amplified neuroblastoma cells, TAF1D functions as a transcriptional activator of G2/M phase genes, including the master cell-cycle regulator CDK1. siRNA knockdown of TAF1D more robustly inhibited proliferation and colony formation in MYCN-amplified versus non-amplified NB cells, suppressed tumor growth in a xenograft mouse model, and RNA-seq revealed downregulation of G2/M transition genes and consequent cell-cycle arrest at G2/M.","method":"Targeted siRNA screening, RNA-seq, xenograft mouse model, cell-cycle analysis, colony formation assay","journal":"Cancer Science","confidence":"Medium","confidence_rationale":"Tier 2 — RNA-seq pathway placement plus in vivo xenograft validation, but single lab and no direct ChIP or promoter binding assay for CDK1","pmids":["37094904"],"is_preprint":false}],"current_model":"TAF1D (TAF(I)41/MGC5306) is an integral subunit of the RNA polymerase I transcription factor SL1, required for SL1 stability at the rDNA promoter, Pol I recruitment, and preinitiation complex formation for ribosomal RNA synthesis; it also interacts with DNA polymerase beta in the nucleus, and in MYCN-amplified neuroblastoma it acts as a transcriptional activator of G2/M cell-cycle genes including CDK1, promoting tumor cell proliferation."},"narrative":{"teleology":[{"year":2004,"claim":"Before TAF1D's role in rDNA transcription was known, its initial characterization revealed it as a nuclear protein that physically interacts with DNA polymerase β — establishing that it participates in nuclear protein networks and that its depletion affects cell growth.","evidence":"Yeast two-hybrid screen with co-immunoprecipitation confirmation, GFP-fusion localization, and siRNA knockdown with cell-cycle analysis in human tumor cell lines","pmids":["15520167"],"confidence":"Medium","gaps":["Functional consequence of the pol β interaction is unknown — no enzymatic or repair assay was performed","Expression claimed to be tumor-specific but tested in limited tissue panel","No reciprocal knockdown of pol β to test whether the interaction is biologically required"]},{"year":2007,"claim":"The central mechanistic question — what TAF1D does at the molecular level — was resolved by showing it is a bona fide SL1 subunit essential for Pol I preinitiation complex formation and rRNA transcription, filling a gap in the composition of the human SL1 complex.","evidence":"Co-purification and reciprocal co-immunoprecipitation with SL1 subunits; immunodepletion from nuclear extracts abolished Pol I transcription (rescued by recombinant SL1); siRNA knockdown displaced SL1 and Pol I from the rDNA promoter by ChIP and reduced pre-rRNA synthesis","pmids":["17318177"],"confidence":"High","gaps":["Structural basis of TAF1D's integration into SL1 is unresolved — no crystal or cryo-EM structure","Whether TAF1D contacts the rDNA promoter directly or only through other SL1 subunits is unknown","Relationship between the pol β interaction and SL1 function was not explored"]},{"year":2023,"claim":"Beyond its canonical role in Pol I transcription, TAF1D was found to function as a context-dependent transcriptional activator of Pol II-transcribed G2/M genes in MYCN-amplified neuroblastoma, revealing a previously unrecognized role in cell-cycle gene regulation and tumor proliferation.","evidence":"siRNA knockdown combined with RNA-seq showing downregulation of G2/M genes including CDK1; xenograft mouse model demonstrating tumor growth suppression; colony formation and cell-cycle arrest assays in MYCN-amplified versus non-amplified neuroblastoma lines","pmids":["37094904"],"confidence":"Medium","gaps":["No direct ChIP or promoter-binding assay for TAF1D at CDK1 or other G2/M gene promoters — activation could be indirect","Whether this Pol II-gene regulatory function operates through SL1 or through an independent mechanism is unknown","Single-lab finding; not independently replicated"]},{"year":null,"claim":"Key open questions include the structural basis of TAF1D within the SL1 complex, whether its pol β interaction is functionally relevant, and by what mechanism it activates Pol II-transcribed cell-cycle genes in neuroblastoma.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of TAF1D within SL1","Pol β interaction function remains uncharacterized","Mechanism linking a Pol I factor to Pol II gene activation is entirely unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140223","term_label":"general transcription initiation factor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,2]}],"complexes":["SL1 (TIF-IB)"],"partners":["POLB","TBP","CDK1"],"other_free_text":[]},"mechanistic_narrative":"TAF1D is an integral subunit of the SL1 complex (also called TIF-IB), the RNA polymerase I-specific transcription factor that nucleates preinitiation complex assembly at the rDNA promoter. Co-purification, reciprocal co-immunoprecipitation, and immunodepletion/reconstitution experiments demonstrate that TAF1D is required for SL1 stability at the rDNA promoter, Pol I recruitment, and pre-rRNA synthesis [PMID:17318177]. TAF1D also interacts with DNA polymerase β in the nucleus, and its knockdown produces anti-proliferative and cell-cycle effects in tumor cells [PMID:15520167]. In MYCN-amplified neuroblastoma, TAF1D acts as a transcriptional activator of G2/M cell-cycle genes including CDK1, and its depletion causes G2/M arrest and suppresses tumor growth in xenograft models [PMID:37094904]."},"prefetch_data":{"uniprot":{"accession":"Q9H5J8","full_name":"TATA box-binding protein-associated factor RNA polymerase I subunit D","aliases":["RNA polymerase I-specific TBP-associated factor 41 kDa","TAFI41","TATA box-binding protein-associated factor 1D","TBP-associated factor 1D","Transcription initiation factor SL1/TIF-IB subunit D"],"length_aa":278,"mass_kda":32.1,"function":"Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9H5J8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TAF1D","classification":"Common Essential","n_dependent_lines":767,"n_total_lines":1208,"dependency_fraction":0.6349337748344371},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000166012","cell_line_id":"CID000851","localizations":[{"compartment":"nucleolus_fc_dfc","grade":3},{"compartment":"nucleoplasm","grade":1}],"interactors":[{"gene":"CSNK2B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000851","total_profiled":1310},"omim":[{"mim_id":"612823","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 1D; TAF1D","url":"https://www.omim.org/entry/612823"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAF1D"},"hgnc":{"alias_symbol":["MGC5306","TAF(I)41"],"prev_symbol":["JOSD3"]},"alphafold":{"accession":"Q9H5J8","domains":[{"cath_id":"-","chopping":"143-196","consensus_level":"medium","plddt":81.8996,"start":143,"end":196}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H5J8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H5J8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H5J8-F1-predicted_aligned_error_v6.png","plddt_mean":62.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAF1D","jax_strain_url":"https://www.jax.org/strain/search?query=TAF1D"},"sequence":{"accession":"Q9H5J8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H5J8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H5J8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H5J8"}},"corpus_meta":[{"pmid":"16169070","id":"PMC_16169070","title":"A human 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Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26496610","id":"PMC_26496610","title":"A human interactome in three quantitative dimensions organized by stoichiometries and abundances.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26496610","citation_count":1015,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25416956","id":"PMC_25416956","title":"A proteome-scale map of the human interactome 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phenotype.","date":"2004","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/15520167","citation_count":10,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"41611887","id":"PMC_41611887","title":"Developmental convergence and divergence in human stem cell models of autism.","date":"2026","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/41611887","citation_count":7,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"40178292","id":"PMC_40178292","title":"RNF112 Facilitates Ubiquitin-Mediated Degradation of c-Myc, Suppressing Proliferation, Migration and Lipid Synthesis in Bladder Cancer.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40178292","citation_count":5,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"37094904","id":"PMC_37094904","title":"TAF1D promotes proliferation by transcriptionally activating G2/M phase-related genes in MYCN-amplified neuroblastoma.","date":"2023","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/37094904","citation_count":4,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"36232890","id":"PMC_36232890","title":"A Degradation Motif in STAU1 Defines a Novel Family of Proteins Involved in Inflammation.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36232890","citation_count":3,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"40593736","id":"PMC_40593736","title":"Human protein interaction networks of ancestral and variant SARS-CoV-2 in organ-specific cells and bodily fluids.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40593736","citation_count":2,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":1512,"output_tokens":34,"usd":0.002523},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.126177,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":14131,"output_tokens":2216,"usd":0.037817},"round2_rules_fired":"R1","round2_stage2":{"model":"claude-opus-4-6","input_tokens":4480,"output_tokens":1393,"usd":0.085837}},"stage1_raw":"```json\n{\n  \"discoveries\": [],\n  \"current_model\": \"No mechanistic findings in the available literature.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries from KEEP papers.\n\n**Classification:**\n\n- [1] Stelzl et al. 2005 (PMID:16169070): Large Y2H network screen — TAF1D may appear as a node but no specific mechanistic finding about TAF1D. EXCLUDE (no specific TAF1D mechanism).\n- [2] Strausberg et al. 2002 (PMID:12477932): MGC cDNA sequencing resource. EXCLUDE (no mechanism).\n- [3] Sowa et al. 2009 (PMID:19615732): DUB interaction landscape — TAF1D may appear as interactor but no specific mechanism. EXCLUDE.\n- [4] Huttlin et al. 2015 (PMID:26186194): BioPlex network. EXCLUDE (no specific TAF1D mechanism).\n- [5] Huttlin et al. 2017 (PMID:28514442): BioPlex 2.0. EXCLUDE.\n- [6] Hein et al. 2015 (PMID:26496610): Quantitative interactome. EXCLUDE.\n- [7] Rolland et al. 2014 (PMID:25416956): Interactome map. EXCLUDE.\n- [8] Luck et al. 2020 (PMID:32296183): HuRI reference interactome. EXCLUDE.\n- [9] Ota et al. 2003 (PMID:14702039): FLJ cDNA sequencing. EXCLUDE.\n- [10] Huttlin et al. 2021 (PMID:33961781): BioPlex 3.0. EXCLUDE.\n- [11] Gaudet et al. 2011 (PMID:21873635): GO annotation methodology. EXCLUDE.\n- [12] Gerhard et al. 2004 (PMID:15489334): MGC resource. EXCLUDE.\n- [13] Cho et al. 2022 (PMID:35271311): OpenCell localization/interaction resource. EXCLUDE (no specific TAF1D mechanism extracted).\n- [14] Vinayagam et al. 2011 (PMID:21900206): Signaling PPI network. EXCLUDE.\n- [15] Lamesch et al. 2007 (PMID:17207965): hORFeome resource. EXCLUDE.\n- [16] Buljan et al. 2020 (PMID:32707033): Kinase interaction network. EXCLUDE.\n- [17] Gorski et al. 2007 (PMID:17318177): TAF(I)41/MGC5306 = TAF1D, novel SL1 component in Pol I transcription. **KEEP.**\n- [18] Uren et al. 2016 (PMID:26760575): hnRNP H1 study. EXCLUDE (alias collision).\n- [19] Wu et al. 2020 (PMID:32513696): RIG-I/TRIM25/ISGylation. EXCLUDE.\n- [20] Witkowski et al. 2022 (PMID:36138187): NUDT21/CD19. EXCLUDE.\n- [21] Liu et al. 2017 (PMID:29150431): MCPH1/APC/C. EXCLUDE.\n- [22] Lai et al. 2011 (PMID:21386990): VHL/p160. EXCLUDE.\n- [23] Yuan et al. 2022 (PMID:36244648): HDLBP/RAF1. EXCLUDE.\n- [24] Vaughan et al. 2022 (PMID:35915203): HECTD1. EXCLUDE.\n- [25] Wang et al. 2004 (PMID:15520167): MGC5306 (=TAF1D) interacts with DNA polymerase beta. **KEEP.**\n- [26] Gordon et al. 2026 (PMID:41611887): ASD stem cell models. EXCLUDE (no specific TAF1D mechanism).\n- [27] Xiong et al. 2025 (PMID:40178292): RNF112/c-Myc. EXCLUDE.\n- [28] Zhang et al. 2023 (PMID:37094904): TAF1D in MYCN-amplified neuroblastoma. **KEEP.**\n- [29] Gonzalez Quesada et al. 2022 (PMID:36232890): STAU1/FPL-motif. EXCLUDE.\n- [30] Broderick et al. 2025 (PMID:40593736): SARS-CoV-2 PPIs. EXCLUDE.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"TAF1D (then called TAF(I)41 / MGC5306) was identified as a novel subunit of the RNA polymerase I transcription factor SL1. It co-purifies and co-immunoprecipitates with SL1, resides at the rDNA promoter in the nucleolus, and is required for Pol I transcription: immunodepletion of TAF(I)41 from nuclear extracts drastically reduces Pol I transcription (rescued by adding recombinant SL1), and siRNA-mediated knockdown in cells causes loss of SL1 from the rDNA promoter, displacement of Pol I from the rDNA, and reduced pre-rRNA synthesis.\",\n      \"method\": \"Co-purification, reciprocal co-immunoprecipitation, immunodepletion/reconstitution in vitro transcription assay, siRNA knockdown with ChIP and pre-rRNA synthesis readout\",\n      \"journal\": \"The EMBO Journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (biochemical purification, reciprocal Co-IP, immunodepletion/reconstitution, siRNA + ChIP) in a single rigorous study\",\n      \"pmids\": [\"17318177\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"TAF1D (MGC5306) was identified as a nuclear protein that interacts with DNA polymerase beta (polβ), including both wild-type polβ and a truncated cancer-associated form (polβΔ), as demonstrated by yeast two-hybrid screening and confirmed by co-immunoprecipitation/Western blot. TAF1D localizes to the nucleus (shown by GFP fusion), is expressed in human carcinomas and tumor cell lines but not normal tissues, and siRNA-mediated knockdown produces anti-growth effects and modulation of cell-cycle events.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation/Western blot, GFP-fusion nuclear localization, siRNA knockdown with cell-cycle analysis\",\n      \"journal\": \"Cancer Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Y2H confirmed by Co-IP and localization, but single lab and limited mechanistic follow-up on polβ interaction function\",\n      \"pmids\": [\"15520167\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In MYCN-amplified neuroblastoma cells, TAF1D functions as a transcriptional activator of G2/M phase genes, including the master cell-cycle regulator CDK1. siRNA knockdown of TAF1D more robustly inhibited proliferation and colony formation in MYCN-amplified versus non-amplified NB cells, suppressed tumor growth in a xenograft mouse model, and RNA-seq revealed downregulation of G2/M transition genes and consequent cell-cycle arrest at G2/M.\",\n      \"method\": \"Targeted siRNA screening, RNA-seq, xenograft mouse model, cell-cycle analysis, colony formation assay\",\n      \"journal\": \"Cancer Science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — RNA-seq pathway placement plus in vivo xenograft validation, but single lab and no direct ChIP or promoter binding assay for CDK1\",\n      \"pmids\": [\"37094904\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAF1D (TAF(I)41/MGC5306) is an integral subunit of the RNA polymerase I transcription factor SL1, required for SL1 stability at the rDNA promoter, Pol I recruitment, and preinitiation complex formation for ribosomal RNA synthesis; it also interacts with DNA polymerase beta in the nucleus, and in MYCN-amplified neuroblastoma it acts as a transcriptional activator of G2/M cell-cycle genes including CDK1, promoting tumor cell proliferation.\"\n}\n```","stage2_raw":"\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"TAF1D is an integral subunit of the SL1 complex (also called TIF-IB), the RNA polymerase I-specific transcription factor that nucleates preinitiation complex assembly at the rDNA promoter. Co-purification, reciprocal co-immunoprecipitation, and immunodepletion/reconstitution experiments demonstrate that TAF1D is required for SL1 stability at the rDNA promoter, Pol I recruitment, and pre-rRNA synthesis [PMID:17318177]. TAF1D also interacts with DNA polymerase β in the nucleus, and its knockdown produces anti-proliferative and cell-cycle effects in tumor cells [PMID:15520167]. In MYCN-amplified neuroblastoma, TAF1D acts as a transcriptional activator of G2/M cell-cycle genes including CDK1, and its depletion causes G2/M arrest and suppresses tumor growth in xenograft models [PMID:37094904].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Before TAF1D's role in rDNA transcription was known, its initial characterization revealed it as a nuclear protein that physically interacts with DNA polymerase β — establishing that it participates in nuclear protein networks and that its depletion affects cell growth.\",\n      \"evidence\": \"Yeast two-hybrid screen with co-immunoprecipitation confirmation, GFP-fusion localization, and siRNA knockdown with cell-cycle analysis in human tumor cell lines\",\n      \"pmids\": [\"15520167\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the pol β interaction is unknown — no enzymatic or repair assay was performed\",\n        \"Expression claimed to be tumor-specific but tested in limited tissue panel\",\n        \"No reciprocal knockdown of pol β to test whether the interaction is biologically required\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The central mechanistic question — what TAF1D does at the molecular level — was resolved by showing it is a bona fide SL1 subunit essential for Pol I preinitiation complex formation and rRNA transcription, filling a gap in the composition of the human SL1 complex.\",\n      \"evidence\": \"Co-purification and reciprocal co-immunoprecipitation with SL1 subunits; immunodepletion from nuclear extracts abolished Pol I transcription (rescued by recombinant SL1); siRNA knockdown displaced SL1 and Pol I from the rDNA promoter by ChIP and reduced pre-rRNA synthesis\",\n      \"pmids\": [\"17318177\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of TAF1D's integration into SL1 is unresolved — no crystal or cryo-EM structure\",\n        \"Whether TAF1D contacts the rDNA promoter directly or only through other SL1 subunits is unknown\",\n        \"Relationship between the pol β interaction and SL1 function was not explored\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Beyond its canonical role in Pol I transcription, TAF1D was found to function as a context-dependent transcriptional activator of Pol II-transcribed G2/M genes in MYCN-amplified neuroblastoma, revealing a previously unrecognized role in cell-cycle gene regulation and tumor proliferation.\",\n      \"evidence\": \"siRNA knockdown combined with RNA-seq showing downregulation of G2/M genes including CDK1; xenograft mouse model demonstrating tumor growth suppression; colony formation and cell-cycle arrest assays in MYCN-amplified versus non-amplified neuroblastoma lines\",\n      \"pmids\": [\"37094904\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct ChIP or promoter-binding assay for TAF1D at CDK1 or other G2/M gene promoters — activation could be indirect\",\n        \"Whether this Pol II-gene regulatory function operates through SL1 or through an independent mechanism is unknown\",\n        \"Single-lab finding; not independently replicated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the structural basis of TAF1D within the SL1 complex, whether its pol β interaction is functionally relevant, and by what mechanism it activates Pol II-transcribed cell-cycle genes in neuroblastoma.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of TAF1D within SL1\",\n        \"Pol β interaction function remains uncharacterized\",\n        \"Mechanism linking a Pol I factor to Pol II gene activation is entirely unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140223\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"SL1 (TIF-IB)\"\n    ],\n    \"partners\": [\n      \"POLB\",\n      \"TBP\",\n      \"CDK1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}