{"gene":"PF3D7_0923000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2005,"finding":"RNA polymerase II synthesizes antisense RNA in P. falciparum nuclei; this antisense transcription is sensitive to the RNA polymerase II inhibitor alpha-amanitin, directly implicating the Pol II machinery (of which RPB3 is a subunit) in antisense RNA production at multiple genomic loci.","method":"Nuclear run-on experiments with single-stranded DNA probes; alpha-amanitin inhibition assay; synchronized parasite nuclei","journal":"RNA (New York, N.Y.)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — establishes a functional activity of the Pol II complex but does not directly interrogate RPB3 (PF3D7_0923000) itself; single lab, single method set directed at the complex rather than this subunit","pmids":["15703443"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"Nascent RNA profiling revealed that RNA polymerase II (the complex containing RPB3) is engaged with promoter regions prior to the major transcriptional burst in the trophozoite stage, indicating that Pol II pausing plays a dominant role in gene regulation during the intraerythrocytic developmental cycle of P. falciparum.","method":"Genome-wide nascent RNA sequencing (GRO-seq / nascent RNA profiling)","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genome-wide functional characterization of Pol II complex behavior but does not directly interrogate RPB3 (PF3D7_0923000) as an individual subunit; single lab","pmids":["28531310"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0923000 (RPB3) is a putative subunit of the P. falciparum RNA polymerase II complex; beyond its membership in this complex—which is responsible for mRNA and antisense RNA synthesis in the parasite nucleus and whose pausing regulates stage-specific gene expression—no mechanistic findings directly and specifically characterizing RPB3 itself are established in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_0923000 (RPB3) is annotated as a putative subunit of the P. falciparum RNA polymerase II complex, and the available corpus characterizes only the activity of that complex rather than RPB3 itself. The Pol II machinery of which RPB3 is a subunit synthesizes antisense RNA at multiple genomic loci in P. falciparum nuclei, an activity sensitive to the Pol II inhibitor alpha-amanitin [PMID:15703443]. Nascent RNA profiling further shows this Pol II complex engaged at promoter regions before the major transcriptional burst of the trophozoite stage, implicating Pol II pausing in stage-specific gene regulation across the intraerythrocytic developmental cycle [PMID:28531310]. No mechanistic finding directly and specifically interrogating RPB3 (PF3D7_0923000) as an individual subunit—its assembly role, interaction partners within the complex, or an RPB3-specific phenotype—has been characterized in the available corpus; the evidence speaks only to the complex.","teleology":[{"year":2005,"claim":"Whether the Pol II machinery is responsible for antisense RNA production in P. falciparum was unresolved; showing alpha-amanitin sensitivity established that the Pol II complex (of which RPB3 is a putative subunit) generates antisense transcripts at multiple loci.","evidence":"Nuclear run-on with single-stranded DNA probes and alpha-amanitin inhibition in synchronized parasite nuclei","pmids":["15703443"],"confidence":"Low","gaps":["Does not directly interrogate RPB3 (PF3D7_0923000); the assay reports the whole Pol II complex","No RPB3-specific contribution to antisense transcription established","No subunit composition or assembly data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"How Pol II activity is timed across the intraerythrocytic cycle was unknown; nascent RNA profiling showed the complex is poised at promoters before the trophozoite transcriptional burst, establishing Pol II pausing as a dominant regulatory mode.","evidence":"Genome-wide nascent RNA sequencing (GRO-seq / nascent RNA profiling) across the intraerythrocytic developmental cycle","pmids":["28531310"],"confidence":"Low","gaps":["Reports Pol II complex behavior, not RPB3-specific function","No demonstration that RPB3 modulates pausing or promoter engagement","No physical or genetic data linking RPB3 to the observed regulatory pattern"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what RPB3 (PF3D7_0923000) contributes as an individual subunit—its role in Pol II assembly, its specific interaction partners, and whether it carries any RPB3-specific regulatory function distinct from the complex.","evidence":"No discovery in the corpus directly interrogates RPB3 as an individual protein","pmids":[],"confidence":"Low","gaps":["No RPB3-specific loss-of-function or localization data","No structural or interaction mapping of RPB3 within Pol II","No evidence distinguishing RPB3 function from bulk Pol II activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RNA polymerase II"],"partners":[],"other_free_text":["The corpus characterizes only the P. falciparum RNA polymerase II complex, of which RPB3 (PF3D7_0923000) is a putative subunit; no finding directly and specifically characterizes RPB3 itself.","Pol II activity implicated in antisense RNA synthesis (alpha-amanitin sensitive) [#0] and in promoter-proximal pausing governing stage-specific gene expression during the intraerythrocytic developmental cycle [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"2690004","id":"PMC_2690004","title":"An enlarged largest subunit of Plasmodium falciparum RNA polymerase II defines conserved and variable RNA polymerase domains.","date":"1989","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2690004","citation_count":71,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"4971014","id":"PMC_4971014","title":"DNA, RNA , and protein synthesis in erythrocytic forms of Plasmodium knowlesi.","date":"1968","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/4971014","citation_count":56,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA","RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15703443","id":"PMC_15703443","title":"RNA polymerase II synthesizes antisense RNA in Plasmodium falciparum.","date":"2005","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/15703443","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28531310","id":"PMC_28531310","title":"Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.","date":"2017","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/28531310","citation_count":52,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"7976752","id":"PMC_7976752","title":"The ribosomal RNA genes of Plasmodium.","date":"1994","source":"Advances in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/7976752","citation_count":46,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15948708","id":"PMC_15948708","title":"DNA-[adenine] methylation in lower eukaryotes.","date":"2005","source":"Biochemistry. Biokhimiia","url":"https://pubmed.ncbi.nlm.nih.gov/15948708","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40626563","id":"PMC_40626563","title":"The ribosomal RNA transcription landscapes of Plasmodium falciparum and related apicomplexan parasites.","date":"2025","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/40626563","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4900,"output_tokens":648,"usd":0.01221,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5295,"output_tokens":1642,"usd":0.033763,"stage2_stop_reason":"end_turn"},"total_usd":0.045973,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"RNA polymerase II synthesizes antisense RNA in P. falciparum nuclei; this antisense transcription is sensitive to the RNA polymerase II inhibitor alpha-amanitin, directly implicating the Pol II machinery (of which RPB3 is a subunit) in antisense RNA production at multiple genomic loci.\",\n      \"method\": \"Nuclear run-on experiments with single-stranded DNA probes; alpha-amanitin inhibition assay; synchronized parasite nuclei\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — establishes a functional activity of the Pol II complex but does not directly interrogate RPB3 (PF3D7_0923000) itself; single lab, single method set directed at the complex rather than this subunit\",\n      \"pmids\": [\"15703443\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nascent RNA profiling revealed that RNA polymerase II (the complex containing RPB3) is engaged with promoter regions prior to the major transcriptional burst in the trophozoite stage, indicating that Pol II pausing plays a dominant role in gene regulation during the intraerythrocytic developmental cycle of P. falciparum.\",\n      \"method\": \"Genome-wide nascent RNA sequencing (GRO-seq / nascent RNA profiling)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genome-wide functional characterization of Pol II complex behavior but does not directly interrogate RPB3 (PF3D7_0923000) as an individual subunit; single lab\",\n      \"pmids\": [\"28531310\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0923000 (RPB3) is a putative subunit of the P. falciparum RNA polymerase II complex; beyond its membership in this complex—which is responsible for mRNA and antisense RNA synthesis in the parasite nucleus and whose pausing regulates stage-specific gene expression—no mechanistic findings directly and specifically characterizing RPB3 itself are established in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0923000 (RPB3) is annotated as a putative subunit of the P. falciparum RNA polymerase II complex, and the available corpus characterizes only the activity of that complex rather than RPB3 itself. The Pol II machinery of which RPB3 is a subunit synthesizes antisense RNA at multiple genomic loci in P. falciparum nuclei, an activity sensitive to the Pol II inhibitor alpha-amanitin [#0]. Nascent RNA profiling further shows this Pol II complex engaged at promoter regions before the major transcriptional burst of the trophozoite stage, implicating Pol II pausing in stage-specific gene regulation across the intraerythrocytic developmental cycle [#1]. No mechanistic finding directly and specifically interrogating RPB3 (PF3D7_0923000) as an individual subunit\\u2014its assembly role, interaction partners within the complex, or an RPB3-specific phenotype\\u2014has been characterized in the available corpus; the evidence speaks only to the complex.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Whether the Pol II machinery is responsible for antisense RNA production in P. falciparum was unresolved; showing alpha-amanitin sensitivity established that the Pol II complex (of which RPB3 is a putative subunit) generates antisense transcripts at multiple loci.\",\n      \"evidence\": \"Nuclear run-on with single-stranded DNA probes and alpha-amanitin inhibition in synchronized parasite nuclei\",\n      \"pmids\": [\"15703443\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Does not directly interrogate RPB3 (PF3D7_0923000); the assay reports the whole Pol II complex\",\n        \"No RPB3-specific contribution to antisense transcription established\",\n        \"No subunit composition or assembly data\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"How Pol II activity is timed across the intraerythrocytic cycle was unknown; nascent RNA profiling showed the complex is poised at promoters before the trophozoite transcriptional burst, establishing Pol II pausing as a dominant regulatory mode.\",\n      \"evidence\": \"Genome-wide nascent RNA sequencing (GRO-seq / nascent RNA profiling) across the intraerythrocytic developmental cycle\",\n      \"pmids\": [\"28531310\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Reports Pol II complex behavior, not RPB3-specific function\",\n        \"No demonstration that RPB3 modulates pausing or promoter engagement\",\n        \"No physical or genetic data linking RPB3 to the observed regulatory pattern\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what RPB3 (PF3D7_0923000) contributes as an individual subunit\\u2014its role in Pol II assembly, its specific interaction partners, and whether it carries any RPB3-specific regulatory function distinct from the complex.\",\n      \"evidence\": \"No discovery in the corpus directly interrogates RPB3 as an individual protein\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No RPB3-specific loss-of-function or localization data\",\n        \"No structural or interaction mapping of RPB3 within Pol II\",\n        \"No evidence distinguishing RPB3 function from bulk Pol II activity\"\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, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006351\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"RNA polymerase II\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"The corpus characterizes only the P. falciparum RNA polymerase II complex, of which RPB3 (PF3D7_0923000) is a putative subunit; no finding directly and specifically characterizes RPB3 itself.\",\n      \"Pol II activity implicated in antisense RNA synthesis (alpha-amanitin sensitive) [#0] and in promoter-proximal pausing governing stage-specific gene expression during the intraerythrocytic developmental cycle [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0923000","name":null,"product":"DNA-directed RNA polymerase II subunit RPB3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0823900","name":null,"product":"DNA-directed RNA polymerase II subunit RPB3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0721000","name":null,"product":"DNA-directed RNA polymerase II subunit RPB3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPB3","evaluation":null}