{"gene":"PF3D7_1359300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2018,"finding":"Recombinant PfDis3 (PF3D7_1359300) exhibited catalytic exoribonuclease activity against single-stranded RNA (ssRNA) in vitro, and was localized to the cytoplasm of P. falciparum asexual-stage parasites by indirect immunofluorescence.","method":"In vitro ssRNA processing assay with recombinant protein; indirect immunofluorescence; Western blot","journal":"The Journal of eukaryotic microbiology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro enzymatic activity assay and direct localization experiment, but single lab and no mutagenesis or replication","pmids":["29664138"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfDis3 (PF3D7_1359300) associates with the RNA exosome core complex, as demonstrated by co-immunoprecipitation, and co-localizes to the cytoplasm of ring-stage parasites.","method":"Co-immunoprecipitation; immunofluorescence assay","journal":"Wiley interdisciplinary reviews. RNA","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP finding reported secondarily in a review abstract body, not independently replicated","pmids":["27230797"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Gene knock-down of PfDis3 (PF3D7_1359300), together with its cofactor PfMtr4, demonstrated that their cooperation plays a major role in the degradation of nascent non-coding RNAs (ns-ncRNAs) in P. falciparum during the intraerythrocytic developmental cycle.","method":"Gene knock-down (inducible); nascent RNA sequencing (rRNA-depleted, stranded RNA-seq); ATAC-seq and ChIP-seq integration","journal":"RNA biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockdown with defined molecular phenotype (ns-ncRNA stabilization) supported by multiple genomic assays, single lab","pmids":["32079470"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1359300 (DIS3) encodes the catalytic exoribonuclease subunit of the RNA exosome complex in P. falciparum; it localizes to the cytoplasm, exhibits 3′–5′ ssRNA degradation activity in vitro, associates with the exosome core complex, and together with the cofactor PfMtr4 is required for degradation of nascent non-coding RNAs during the intraerythrocytic developmental cycle."},"narrative":{"mechanistic_narrative":"PF3D7_1359300 (DIS3) encodes the catalytic exoribonuclease subunit of the RNA exosome in Plasmodium falciparum, functioning in the turnover of non-coding RNAs during the intraerythrocytic developmental cycle [PMID:29664138, PMID:32079470]. The recombinant protein degrades single-stranded RNA in vitro and localizes to the parasite cytoplasm in asexual-stage parasites, where it associates with the RNA exosome core complex [PMID:29664138, PMID:27230797]. Together with its cofactor PfMtr4, DIS3 is required for the degradation of nascent non-coding RNAs (ns-ncRNAs), establishing its role in controlling the parasite's non-coding transcriptome [PMID:32079470]. Beyond its 3′–5′ ssRNA exonuclease activity, cytoplasmic localization, exosome association, and ns-ncRNA turnover function, no further mechanistic detail—including structural basis, substrate specificity determinants, or catalytic residues—has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"To establish whether PF3D7_1359300 is an active nuclease and where it acts, the recombinant protein was tested biochemically and localized in parasites, defining it as a cytoplasmic ssRNA-degrading exoribonuclease.","evidence":"In vitro ssRNA processing assay with recombinant protein plus indirect immunofluorescence and Western blot in P. falciparum asexual stages","pmids":["29664138"],"confidence":"Medium","gaps":["No mutagenesis to confirm catalytic residues","Substrate specificity beyond generic ssRNA not defined","Single lab, no replication"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To determine whether PF3D7_1359300 operates within the exosome machinery rather than in isolation, physical association was tested, placing it in the RNA exosome core complex in the cytoplasm.","evidence":"Co-immunoprecipitation and immunofluorescence in ring-stage P. falciparum parasites","pmids":["27230797"],"confidence":"Low","gaps":["Single Co-IP reported secondarily in a review, not independently replicated","Stoichiometry and identity of core subunits not resolved","No reciprocal pull-down"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To connect the enzyme to a cellular RNA-regulatory function, inducible knock-down defined its physiological substrates, showing that DIS3 and its cofactor PfMtr4 drive degradation of nascent non-coding RNAs during the intraerythrocytic cycle.","evidence":"Inducible gene knock-down with rRNA-depleted stranded nascent RNA-seq integrated with ATAC-seq and ChIP-seq in P. falciparum","pmids":["32079470"],"confidence":"Medium","gaps":["Direct enzyme-substrate contacts on ns-ncRNAs not shown","Contribution of DIS3 versus PfMtr4 not separated","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The catalytic mechanism, structural organization within the exosome, and full substrate repertoire of PF3D7_1359300 remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure or catalytic-residue mutagenesis","No comprehensive substrate map beyond ns-ncRNAs","Role in parasite viability and drug-target potential not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RNA exosome core complex"],"partners":["PFMTR4"],"other_free_text":["Knock-down of DIS3 together with PfMtr4 stabilizes nascent non-coding RNAs during the intraerythrocytic developmental cycle [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32079470","id":"PMC_32079470","title":"The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.","date":"2020","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/32079470","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfDIS3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29664138","id":"PMC_29664138","title":"Characterization of the Catalytic Subunits of the RNA Exosome-like Complex in Plasmodium falciparum.","date":"2018","source":"The Journal of eukaryotic microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29664138","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfDIS3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32487761","id":"","title":"Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32487761","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DIS3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27230797","id":"","title":"Translational regulation in blood stages of the malaria parasite Plasmodium spp.: systems-wide studies pave the way.","date":"2016","source":"Wiley interdisciplinary reviews. RNA","url":"https://pubmed.ncbi.nlm.nih.gov/27230797","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DIS3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27911910","id":"","title":"Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27911910","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DIS3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7737,"output_tokens":852,"usd":0.017996,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5564,"output_tokens":1823,"usd":0.036698,"stage2_stop_reason":"end_turn"},"total_usd":0.054694,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Recombinant PfDis3 (PF3D7_1359300) exhibited catalytic exoribonuclease activity against single-stranded RNA (ssRNA) in vitro, and was localized to the cytoplasm of P. falciparum asexual-stage parasites by indirect immunofluorescence.\",\n      \"method\": \"In vitro ssRNA processing assay with recombinant protein; indirect immunofluorescence; Western blot\",\n      \"journal\": \"The Journal of eukaryotic microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro enzymatic activity assay and direct localization experiment, but single lab and no mutagenesis or replication\",\n      \"pmids\": [\"29664138\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfDis3 (PF3D7_1359300) associates with the RNA exosome core complex, as demonstrated by co-immunoprecipitation, and co-localizes to the cytoplasm of ring-stage parasites.\",\n      \"method\": \"Co-immunoprecipitation; immunofluorescence assay\",\n      \"journal\": \"Wiley interdisciplinary reviews. RNA\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP finding reported secondarily in a review abstract body, not independently replicated\",\n      \"pmids\": [\"27230797\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Gene knock-down of PfDis3 (PF3D7_1359300), together with its cofactor PfMtr4, demonstrated that their cooperation plays a major role in the degradation of nascent non-coding RNAs (ns-ncRNAs) in P. falciparum during the intraerythrocytic developmental cycle.\",\n      \"method\": \"Gene knock-down (inducible); nascent RNA sequencing (rRNA-depleted, stranded RNA-seq); ATAC-seq and ChIP-seq integration\",\n      \"journal\": \"RNA biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown with defined molecular phenotype (ns-ncRNA stabilization) supported by multiple genomic assays, single lab\",\n      \"pmids\": [\"32079470\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1359300 (DIS3) encodes the catalytic exoribonuclease subunit of the RNA exosome complex in P. falciparum; it localizes to the cytoplasm, exhibits 3′–5′ ssRNA degradation activity in vitro, associates with the exosome core complex, and together with the cofactor PfMtr4 is required for degradation of nascent non-coding RNAs during the intraerythrocytic developmental cycle.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_1359300 (DIS3) encodes the catalytic exoribonuclease subunit of the RNA exosome in Plasmodium falciparum, functioning in the turnover of non-coding RNAs during the intraerythrocytic developmental cycle [#0, #2]. The recombinant protein degrades single-stranded RNA in vitro and localizes to the parasite cytoplasm in asexual-stage parasites, where it associates with the RNA exosome core complex [#0, #1]. Together with its cofactor PfMtr4, DIS3 is required for the degradation of nascent non-coding RNAs (ns-ncRNAs), establishing its role in controlling the parasite's non-coding transcriptome [#2]. Beyond its 3\\u2032\\u20135\\u2032 ssRNA exonuclease activity, cytoplasmic localization, exosome association, and ns-ncRNA turnover function, no further mechanistic detail\\u2014including structural basis, substrate specificity determinants, or catalytic residues\\u2014has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"To establish whether PF3D7_1359300 is an active nuclease and where it acts, the recombinant protein was tested biochemically and localized in parasites, defining it as a cytoplasmic ssRNA-degrading exoribonuclease.\",\n      \"evidence\": \"In vitro ssRNA processing assay with recombinant protein plus indirect immunofluorescence and Western blot in P. falciparum asexual stages\",\n      \"pmids\": [\"29664138\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mutagenesis to confirm catalytic residues\", \"Substrate specificity beyond generic ssRNA not defined\", \"Single lab, no replication\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To determine whether PF3D7_1359300 operates within the exosome machinery rather than in isolation, physical association was tested, placing it in the RNA exosome core complex in the cytoplasm.\",\n      \"evidence\": \"Co-immunoprecipitation and immunofluorescence in ring-stage P. falciparum parasites\",\n      \"pmids\": [\"27230797\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP reported secondarily in a review, not independently replicated\", \"Stoichiometry and identity of core subunits not resolved\", \"No reciprocal pull-down\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To connect the enzyme to a cellular RNA-regulatory function, inducible knock-down defined its physiological substrates, showing that DIS3 and its cofactor PfMtr4 drive degradation of nascent non-coding RNAs during the intraerythrocytic cycle.\",\n      \"evidence\": \"Inducible gene knock-down with rRNA-depleted stranded nascent RNA-seq integrated with ATAC-seq and ChIP-seq in P. falciparum\",\n      \"pmids\": [\"32079470\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct enzyme-substrate contacts on ns-ncRNAs not shown\", \"Contribution of DIS3 versus PfMtr4 not separated\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic mechanism, structural organization within the exosome, and full substrate repertoire of PF3D7_1359300 remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure or catalytic-residue mutagenesis\", \"No comprehensive substrate map beyond ns-ncRNAs\", \"Role in parasite viability and drug-target potential not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0000175\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0004532\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003727\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0000178\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071028\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0006401\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"RNA exosome core complex\"],\n    \"partners\": [\"PfMtr4\"],\n    \"other_free_text\": [\n      \"Knock-down of DIS3 together with PfMtr4 stabilizes nascent non-coding RNAs during the intraerythrocytic developmental cycle [#2]\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1359300","name":null,"product":"exosome complex exonuclease RRP44","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1135600","name":null,"product":"exosome complex exonuclease RRP44, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1112000","name":null,"product":"exosome complex exonuclease RRP44, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DIS3","evaluation":null}