{"gene":"CSTF1","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2011,"finding":"p53 C-terminus associates with CstF1 (CstF-50) and BARD1 in complexes from UV-treated cell extracts, and p53 inhibits the 3' cleavage step of polyadenylation in vitro; a tumor-associated p53 mutation decreases interaction with CstF and BARD1 and reduces UV-induced inhibition of 3' processing, which is restored by wild-type p53 expression.","method":"Co-immunoprecipitation from UV-treated cell extracts, in vitro 3' cleavage assay, tumor-associated p53 mutant analysis with rescue by wild-type p53 expression","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and in vitro cleavage assay with mutant validation in single lab","pmids":["21383700"],"is_preprint":false},{"year":2018,"finding":"CstF-50 (CSTF1) is a structural subunit of the trimeric CstF complex (with CstF-64/CSTF2 and CstF-77/CSTF3) required for recognition of the correct 3'-end processing site and cleavage/polyadenylation of pre-mRNA; CstF-64 is the RNA-binding subunit of this complex.","method":"Genetic knockout of the paralog Cstf2t combined with RNA-seq and A-seq characterization of polyadenylation in male germ cells (establishes the subunit composition and functional assignment of CSTF1 within the complex by context)","journal":"Andrology","confidence":"Medium","confidence_rationale":"Tier 3 / Strong — subunit role inferred from established complex biology described in the paper; consistent with multiple papers in corpus","pmids":["29673127"],"is_preprint":false},{"year":2022,"finding":"CSTF1 (CstF-50) is physically associated with human U2 snRNA genes, as shown by CRISPR-deadCas9-mediated genomic pull-down (CAPTURE), placing it at snRNA gene loci alongside other polyadenylation and transcription factors.","method":"CAPTURE (deadCas9-mediated chromatin affinity purification) of tandem U2 snRNA gene loci in human cells followed by mass spectrometry","journal":"Biomolecules","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single pull-down method, no functional consequence specifically linked to CSTF1 at these loci","pmids":["35625631"],"is_preprint":false}],"current_model":"CSTF1 (CstF-50) is a non-RNA-binding structural subunit of the trimeric CstF complex that is required for mRNA 3'-end cleavage and polyadenylation; following DNA damage, it participates in a p53–BARD1–CstF complex that inhibits the 3' cleavage step in vitro, linking RNA 3'-end processing to the p53-mediated DNA damage response."},"narrative":{"mechanistic_narrative":"CSTF1 (CstF-50) is a structural subunit of the trimeric cleavage stimulation factor (CstF) complex, where together with the RNA-binding subunit CstF-64/CSTF2 and CstF-77/CSTF3 it is required for recognition of the correct 3'-end processing site and for cleavage/polyadenylation of pre-mRNA [PMID:29673127]. Beyond its core role in constitutive 3'-end processing, CSTF1 links RNA 3'-end maturation to the DNA damage response: following UV irradiation, the p53 C-terminus associates with CstF-50 and BARD1, and this p53–BARD1–CstF complex inhibits the 3' cleavage step of polyadenylation in vitro, an inhibition that is lost with a tumor-associated p53 mutation that weakens p53 binding to CstF and BARD1 and is restored by wild-type p53 [PMID:21383700]. CSTF1 has also been localized to U2 snRNA gene loci by genomic affinity purification [PMID:35625631].","teleology":[{"year":2011,"claim":"Established that 3'-end processing is coupled to the DNA damage response by showing CstF-50 forms a regulatory complex with p53 and BARD1 that suppresses pre-mRNA cleavage after UV damage.","evidence":"Co-immunoprecipitation from UV-treated cell extracts and in vitro 3' cleavage assay, with a tumor-associated p53 mutant and wild-type rescue","pmids":["21383700"],"confidence":"Medium","gaps":["The structural basis and direct binding interface between CstF-50 and p53/BARD1 is not resolved","Whether this inhibition occurs on endogenous transcripts genome-wide in vivo is not addressed","The downstream consequence of cleavage inhibition for DNA repair or cell fate is not established"]},{"year":2018,"claim":"Defined CSTF1/CstF-50 as a non-RNA-binding structural subunit of the trimeric CstF complex required for correct poly(A) site recognition and cleavage, with CstF-64 serving as the RNA-binding subunit.","evidence":"Knockout of the paralog Cstf2t with RNA-seq and A-seq profiling of polyadenylation in male germ cells, establishing complex composition and CSTF1's role by context","pmids":["29673127"],"confidence":"Medium","gaps":["Direct functional contribution of CSTF1 itself (versus the complex) was inferred by context, not isolated by CSTF1 perturbation","Stoichiometry and assembly determinants of the trimer are not addressed here"]},{"year":2022,"claim":"Placed CSTF1 at U2 snRNA gene loci, raising the possibility that the polyadenylation machinery participates in snRNA gene transcription/processing.","evidence":"CAPTURE (deadCas9-mediated chromatin affinity purification) of tandem U2 snRNA gene loci followed by mass spectrometry in human cells","pmids":["35625631"],"confidence":"Low","gaps":["Single-lab, single pull-down method with no functional consequence linked specifically to CSTF1 at these loci","Whether the association is direct or mediated through the CstF complex is unknown"]},{"year":null,"claim":"The molecular mechanism by which CSTF1 specifically contributes to poly(A) site selection within the CstF trimer, and how its DNA-damage-coupled regulation reshapes transcriptome-wide 3'-end processing, remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structure of the human CstF trimer or of CSTF1 in complex with p53/BARD1 in the corpus","No CSTF1-specific loss-of-function transcriptome study","Functional role at snRNA loci uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[1]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","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":[1]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,2]}],"complexes":["CstF complex"],"partners":["CSTF2","CSTF3","TP53","BARD1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q05048","full_name":"Cleavage stimulation factor subunit 1","aliases":["CF-1 50 kDa subunit","Cleavage stimulation factor 50 kDa subunit","CSTF 50 kDa subunit","CstF-50"],"length_aa":431,"mass_kda":48.4,"function":"One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs (PubMed:10669729). May be responsible for the interaction of CSTF with other factors to form a stable complex on the pre-mRNA (PubMed:10669729)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q05048/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/CSTF1","classification":"Common Essential","n_dependent_lines":1163,"n_total_lines":1208,"dependency_fraction":0.9627483443708609},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CPSF6","stoichiometry":0.2},{"gene":"RBM14","stoichiometry":0.2},{"gene":"SNRPA","stoichiometry":0.2},{"gene":"TOP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CSTF1","total_profiled":1310},"omim":[{"mim_id":"602388","title":"SYMPLEKIN; SYMPK","url":"https://www.omim.org/entry/602388"},{"mim_id":"601593","title":"BRCA1-ASSOCIATED RING DOMAIN 1; BARD1","url":"https://www.omim.org/entry/601593"},{"mim_id":"600369","title":"CLEAVAGE STIMULATION FACTOR, 3-PRIME PRE-RNA, SUBUNIT 1, 50-KD; CSTF1","url":"https://www.omim.org/entry/600369"},{"mim_id":"600367","title":"CLEAVAGE STIMULATION FACTOR, 3-PRIME PRE-RNA, SUBUNIT 3, 77-KD; CSTF3","url":"https://www.omim.org/entry/600367"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CSTF1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q05048","domains":[{"cath_id":"1.20.960.50","chopping":"7-67","consensus_level":"high","plddt":83.9861,"start":7,"end":67},{"cath_id":"2.130.10.10","chopping":"99-424","consensus_level":"high","plddt":95.4232,"start":99,"end":424}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q05048","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q05048-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q05048-F1-predicted_aligned_error_v6.png","plddt_mean":90.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CSTF1","jax_strain_url":"https://www.jax.org/strain/search?query=CSTF1"},"sequence":{"accession":"Q05048","fasta_url":"https://rest.uniprot.org/uniprotkb/Q05048.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q05048/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q05048"}},"corpus_meta":[{"pmid":"25830658","id":"PMC_25830658","title":"Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25830658","citation_count":40,"is_preprint":false},{"pmid":"21383700","id":"PMC_21383700","title":"p53 inhibits mRNA 3' processing through its interaction with the CstF/BARD1 complex.","date":"2011","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/21383700","citation_count":32,"is_preprint":false},{"pmid":"29673127","id":"PMC_29673127","title":"Cstf2t Regulates expression of histones and histone-like proteins in male germ cells.","date":"2018","source":"Andrology","url":"https://pubmed.ncbi.nlm.nih.gov/29673127","citation_count":18,"is_preprint":false},{"pmid":"25836033","id":"PMC_25836033","title":"Anammox cultivation in a closed sponge-bed trickling filter.","date":"2015","source":"Bioresource technology","url":"https://pubmed.ncbi.nlm.nih.gov/25836033","citation_count":16,"is_preprint":false},{"pmid":"38730662","id":"PMC_38730662","title":"Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors.","date":"2024","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/38730662","citation_count":11,"is_preprint":false},{"pmid":"36623676","id":"PMC_36623676","title":"MiR-125b and SATB1-AS1 might be shear stress-mediated therapeutic targets.","date":"2023","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/36623676","citation_count":8,"is_preprint":false},{"pmid":"40215969","id":"PMC_40215969","title":"Computational and functional prioritization identifies genes that rescue behavior and reduce tau protein in fly and human cell models of Alzheimer disease.","date":"2025","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40215969","citation_count":5,"is_preprint":false},{"pmid":"35625631","id":"PMC_35625631","title":"CAPTURE of the Human U2 snRNA Genes Expands the Repertoire of Associated Factors.","date":"2022","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/35625631","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6806,"output_tokens":871,"usd":0.016741,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7268,"output_tokens":1730,"usd":0.039795,"stage2_stop_reason":"end_turn"},"total_usd":0.056536,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"p53 C-terminus associates with CstF1 (CstF-50) and BARD1 in complexes from UV-treated cell extracts, and p53 inhibits the 3' cleavage step of polyadenylation in vitro; a tumor-associated p53 mutation decreases interaction with CstF and BARD1 and reduces UV-induced inhibition of 3' processing, which is restored by wild-type p53 expression.\",\n      \"method\": \"Co-immunoprecipitation from UV-treated cell extracts, in vitro 3' cleavage assay, tumor-associated p53 mutant analysis with rescue by wild-type p53 expression\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and in vitro cleavage assay with mutant validation in single lab\",\n      \"pmids\": [\"21383700\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CstF-50 (CSTF1) is a structural subunit of the trimeric CstF complex (with CstF-64/CSTF2 and CstF-77/CSTF3) required for recognition of the correct 3'-end processing site and cleavage/polyadenylation of pre-mRNA; CstF-64 is the RNA-binding subunit of this complex.\",\n      \"method\": \"Genetic knockout of the paralog Cstf2t combined with RNA-seq and A-seq characterization of polyadenylation in male germ cells (establishes the subunit composition and functional assignment of CSTF1 within the complex by context)\",\n      \"journal\": \"Andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Strong — subunit role inferred from established complex biology described in the paper; consistent with multiple papers in corpus\",\n      \"pmids\": [\"29673127\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CSTF1 (CstF-50) is physically associated with human U2 snRNA genes, as shown by CRISPR-deadCas9-mediated genomic pull-down (CAPTURE), placing it at snRNA gene loci alongside other polyadenylation and transcription factors.\",\n      \"method\": \"CAPTURE (deadCas9-mediated chromatin affinity purification) of tandem U2 snRNA gene loci in human cells followed by mass spectrometry\",\n      \"journal\": \"Biomolecules\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pull-down method, no functional consequence specifically linked to CSTF1 at these loci\",\n      \"pmids\": [\"35625631\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CSTF1 (CstF-50) is a non-RNA-binding structural subunit of the trimeric CstF complex that is required for mRNA 3'-end cleavage and polyadenylation; following DNA damage, it participates in a p53–BARD1–CstF complex that inhibits the 3' cleavage step in vitro, linking RNA 3'-end processing to the p53-mediated DNA damage response.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CSTF1 (CstF-50) is a structural subunit of the trimeric cleavage stimulation factor (CstF) complex, where together with the RNA-binding subunit CstF-64/CSTF2 and CstF-77/CSTF3 it is required for recognition of the correct 3'-end processing site and for cleavage/polyadenylation of pre-mRNA [#1]. Beyond its core role in constitutive 3'-end processing, CSTF1 links RNA 3'-end maturation to the DNA damage response: following UV irradiation, the p53 C-terminus associates with CstF-50 and BARD1, and this p53–BARD1–CstF complex inhibits the 3' cleavage step of polyadenylation in vitro, an inhibition that is lost with a tumor-associated p53 mutation that weakens p53 binding to CstF and BARD1 and is restored by wild-type p53 [#0]. CSTF1 has also been localized to U2 snRNA gene loci by genomic affinity purification [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established that 3'-end processing is coupled to the DNA damage response by showing CstF-50 forms a regulatory complex with p53 and BARD1 that suppresses pre-mRNA cleavage after UV damage.\",\n      \"evidence\": \"Co-immunoprecipitation from UV-treated cell extracts and in vitro 3' cleavage assay, with a tumor-associated p53 mutant and wild-type rescue\",\n      \"pmids\": [\"21383700\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The structural basis and direct binding interface between CstF-50 and p53/BARD1 is not resolved\",\n        \"Whether this inhibition occurs on endogenous transcripts genome-wide in vivo is not addressed\",\n        \"The downstream consequence of cleavage inhibition for DNA repair or cell fate is not established\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined CSTF1/CstF-50 as a non-RNA-binding structural subunit of the trimeric CstF complex required for correct poly(A) site recognition and cleavage, with CstF-64 serving as the RNA-binding subunit.\",\n      \"evidence\": \"Knockout of the paralog Cstf2t with RNA-seq and A-seq profiling of polyadenylation in male germ cells, establishing complex composition and CSTF1's role by context\",\n      \"pmids\": [\"29673127\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct functional contribution of CSTF1 itself (versus the complex) was inferred by context, not isolated by CSTF1 perturbation\",\n        \"Stoichiometry and assembly determinants of the trimer are not addressed here\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed CSTF1 at U2 snRNA gene loci, raising the possibility that the polyadenylation machinery participates in snRNA gene transcription/processing.\",\n      \"evidence\": \"CAPTURE (deadCas9-mediated chromatin affinity purification) of tandem U2 snRNA gene loci followed by mass spectrometry in human cells\",\n      \"pmids\": [\"35625631\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single-lab, single pull-down method with no functional consequence linked specifically to CSTF1 at these loci\",\n        \"Whether the association is direct or mediated through the CstF complex is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular mechanism by which CSTF1 specifically contributes to poly(A) site selection within the CstF trimer, and how its DNA-damage-coupled regulation reshapes transcriptome-wide 3'-end processing, remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structure of the human CstF trimer or of CSTF1 in complex with p53/BARD1 in the corpus\",\n        \"No CSTF1-specific loss-of-function transcriptome study\",\n        \"Functional role at snRNA loci uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0098772\", \"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\": [1]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\"CstF complex\"],\n    \"partners\": [\"CSTF2\", \"CSTF3\", \"TP53\", \"BARD1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}