{"gene":"PF3D7_0314700","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2017,"finding":"RNF1 (PfRNF1) protein is expressed predominantly in the sexual stages of P. falciparum, with peak expression in stage II gametocytes, where it localizes to both the nucleus and cytoplasm, as determined by immunochemistry.","method":"Immunochemistry / immunofluorescence localization in gametocyte stages","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct immunochemistry localization experiment, single lab, single method, but consistent with transcriptional data","pmids":["28791254"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The RNF1 (PfRNF1) gene is upregulated by histone hyperacetylation: treatment with the histone deacetylase inhibitor trichostatin A (TSA) increased PfRNF1 transcript and protein levels in mature gametocytes, and chromatin immunoprecipitation (ChIP) showed that the Pfrnf1 promoter and coding regions are associated with acetylated histones.","method":"Microarray transcriptomics + immunochemistry (protein level) + chromatin immunoprecipitation (ChIP) of acetylated histones at Pfrnf1 locus","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — two orthogonal methods (ChIP and transcriptomics/immunochemistry), single lab","pmids":["28791254"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, RNF1 (PF3D7_0314700), a putative RING-domain E3 ubiquitin ligase, is expressed predominantly in sexual (gametocyte) stages with peak levels at stage II, where it localizes to the nucleus and cytoplasm; its expression is positively regulated by histone acetylation at its promoter and coding regions, as demonstrated by ChIP and HDAC-inhibitor experiments."},"narrative":{"mechanistic_narrative":"RNF1 (PF3D7_0314700) is a putative RING-domain E3 ubiquitin ligase of Plasmodium falciparum whose characterized biology is confined to its expression, localization, and transcriptional regulation during sexual development. The protein is expressed predominantly in sexual (gametocyte) stages, peaking at stage II, and localizes to both the nucleus and cytoplasm [PMID:28791254]. Its expression is under epigenetic control: histone hyperacetylation induced by the histone deacetylase inhibitor trichostatin A elevates both transcript and protein levels in mature gametocytes, and chromatin immunoprecipitation places acetylated histones at the Pfrnf1 promoter and coding regions, indicating that acetylation-associated chromatin positively regulates RNF1 expression [PMID:28791254]. Beyond this expression and regulatory profile, no substrate, catalytic activity, interaction partner, or functional phenotype for RNF1 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Establishing when and where RNF1 acts required defining its stage specificity and subcellular distribution, which was unknown; the finding placed RNF1 in sexual-stage parasites with dual nuclear/cytoplasmic localization.","evidence":"Immunochemistry/immunofluorescence localization across gametocyte stages in P. falciparum","pmids":["28791254"],"confidence":"Medium","gaps":["No substrate or ubiquitin-ligase activity demonstrated for RNF1","No functional phenotype (e.g. knockout or knockdown effect on gametocytogenesis) established","Dual localization not resolved to specific compartments or interaction partners"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"How RNF1 expression is controlled was unknown; showing that HDAC inhibition raises RNF1 levels and that acetylated histones occupy its locus established that RNF1 is positively regulated by histone acetylation.","evidence":"Microarray transcriptomics, immunochemistry, and ChIP of acetylated histones at the Pfrnf1 locus after trichostatin A treatment in P. falciparum","pmids":["28791254"],"confidence":"Medium","gaps":["Specific histone marks and writer/eraser enzymes responsible not identified","Whether acetylation-driven induction alters RNF1 function or only abundance is unknown","Downstream consequences of RNF1 upregulation for gametocyte biology not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The core biochemical role of RNF1 remains unresolved: no ubiquitin-ligase activity, substrate, interaction partner, or loss-of-function phenotype has been defined in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No demonstration of E3 ubiquitin ligase catalytic activity","No identified ubiquitination substrates or complex partners","No genetic evidence for a role in gametocyte development or transmission"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Putative RING-domain E3 ubiquitin ligase (annotation-level; no catalytic activity demonstrated in the corpus)","Expressed predominantly in sexual (gametocyte) stages, peaking at stage II [#0]","Expression positively regulated by histone acetylation; induced by the HDAC inhibitor trichostatin A, with acetylated histones at the Pfrnf1 promoter and coding regions [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28791254","id":"PMC_28791254","title":"Transcriptional Profiling Defines Histone Acetylation as a Regulator of Gene Expression during Human-to-Mosquito Transmission of the Malaria Parasite Plasmodium falciparum.","date":"2017","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28791254","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfRNF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34418264","id":"PMC_34418264","title":"Zinc finger proteins of Plasmodium falciparum.","date":"2021","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34418264","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RING"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40592953","id":"PMC_40592953","title":"Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40592953","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RING"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40035193","id":"PMC_40035193","title":"Understanding the Role of RING-Between-RING E3 Ligase of the Human Malaria Parasite.","date":"2025","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/40035193","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RING"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4892,"output_tokens":1034,"usd":0.015093,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5246,"output_tokens":1539,"usd":0.032352,"stage2_stop_reason":"end_turn"},"total_usd":0.047445,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully evaluate each paper to determine if it is about PF3D7_0314700 (RNF1), a RING finger protein in P. falciparum.\n\n**Paper [1] (PMID:28791254):** Describes PfRNF1 (the gene product of PF3D7_0314700) directly — localization to nucleus and cytoplasm in stage II gametocytes, expression in sexual stages, and regulation by histone acetylation. This is directly about PF3D7_0314700. ✓\n\n**Paper [2] (PMID:34418264):** This is a review of zinc finger proteins in P. falciparum — a broad catalog/review. It mentions RING finger proteins generally but doesn't appear to establish specific mechanistic findings about PF3D7_0314700 specifically. EXCLUDE as catalog/review.\n\n**Paper [3] (PMID:40592953):** Describes Cullin-RING-Ligase complexes in P. falciparum — focuses on PfCullin1 and PfCullin4 complexes. Does not specifically characterize PF3D7_0314700/RNF1. EXCLUDE.\n\n**Paper [4] (PMID:40035193):** Describes a \"RING-between-RING (RBR) E3 ligase\" in P. falciparum — this is a different E3 ligase (RBR type), not PF3D7_0314700/RNF1 which is a simple RING finger protein. EXCLUDE.\n\nOnly Paper [1] contains mechanistic findings about PF3D7_0314700.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"RNF1 (PfRNF1) protein is expressed predominantly in the sexual stages of P. falciparum, with peak expression in stage II gametocytes, where it localizes to both the nucleus and cytoplasm, as determined by immunochemistry.\",\n      \"method\": \"Immunochemistry / immunofluorescence localization in gametocyte stages\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct immunochemistry localization experiment, single lab, single method, but consistent with transcriptional data\",\n      \"pmids\": [\"28791254\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The RNF1 (PfRNF1) gene is upregulated by histone hyperacetylation: treatment with the histone deacetylase inhibitor trichostatin A (TSA) increased PfRNF1 transcript and protein levels in mature gametocytes, and chromatin immunoprecipitation (ChIP) showed that the Pfrnf1 promoter and coding regions are associated with acetylated histones.\",\n      \"method\": \"Microarray transcriptomics + immunochemistry (protein level) + chromatin immunoprecipitation (ChIP) of acetylated histones at Pfrnf1 locus\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — two orthogonal methods (ChIP and transcriptomics/immunochemistry), single lab\",\n      \"pmids\": [\"28791254\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, RNF1 (PF3D7_0314700), a putative RING-domain E3 ubiquitin ligase, is expressed predominantly in sexual (gametocyte) stages with peak levels at stage II, where it localizes to the nucleus and cytoplasm; its expression is positively regulated by histone acetylation at its promoter and coding regions, as demonstrated by ChIP and HDAC-inhibitor experiments.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RNF1 (PF3D7_0314700) is a putative RING-domain E3 ubiquitin ligase of Plasmodium falciparum whose characterized biology is confined to its expression, localization, and transcriptional regulation during sexual development. The protein is expressed predominantly in sexual (gametocyte) stages, peaking at stage II, and localizes to both the nucleus and cytoplasm [#0]. Its expression is under epigenetic control: histone hyperacetylation induced by the histone deacetylase inhibitor trichostatin A elevates both transcript and protein levels in mature gametocytes, and chromatin immunoprecipitation places acetylated histones at the Pfrnf1 promoter and coding regions, indicating that acetylation-associated chromatin positively regulates RNF1 expression [#1]. Beyond this expression and regulatory profile, no substrate, catalytic activity, interaction partner, or functional phenotype for RNF1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing when and where RNF1 acts required defining its stage specificity and subcellular distribution, which was unknown; the finding placed RNF1 in sexual-stage parasites with dual nuclear/cytoplasmic localization.\",\n      \"evidence\": \"Immunochemistry/immunofluorescence localization across gametocyte stages in P. falciparum\",\n      \"pmids\": [\"28791254\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No substrate or ubiquitin-ligase activity demonstrated for RNF1\",\n        \"No functional phenotype (e.g. knockout or knockdown effect on gametocytogenesis) established\",\n        \"Dual localization not resolved to specific compartments or interaction partners\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"How RNF1 expression is controlled was unknown; showing that HDAC inhibition raises RNF1 levels and that acetylated histones occupy its locus established that RNF1 is positively regulated by histone acetylation.\",\n      \"evidence\": \"Microarray transcriptomics, immunochemistry, and ChIP of acetylated histones at the Pfrnf1 locus after trichostatin A treatment in P. falciparum\",\n      \"pmids\": [\"28791254\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific histone marks and writer/eraser enzymes responsible not identified\",\n        \"Whether acetylation-driven induction alters RNF1 function or only abundance is unknown\",\n        \"Downstream consequences of RNF1 upregulation for gametocyte biology not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The core biochemical role of RNF1 remains unresolved: no ubiquitin-ligase activity, substrate, interaction partner, or loss-of-function phenotype has been defined in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No demonstration of E3 ubiquitin ligase catalytic activity\",\n        \"No identified ubiquitination substrates or complex partners\",\n        \"No genetic evidence for a role in gametocyte development or transmission\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Putative RING-domain E3 ubiquitin ligase (annotation-level; no catalytic activity demonstrated in the corpus)\",\n      \"Expressed predominantly in sexual (gametocyte) stages, peaking at stage II [#0]\",\n      \"Expression positively regulated by histone acetylation; induced by the HDAC inhibitor trichostatin A, with acetylated histones at the Pfrnf1 promoter and coding regions [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0314700","name":null,"product":"RING finger protein RNF1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0412400","name":null,"product":"RING finger protein RNF1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0827400","name":null,"product":"RING finger protein RNF1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RNF1","evaluation":null}