{"gene":"TG_270380","gene_symbol":"RPS13","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2006,"finding":"The T. gondii RPS13 promoter has a single major transcriptional start site, and integration of four tet operator elements 23–43 bp upstream of this start site results in maximal transcriptional repression (88-fold), establishing the promoter architecture required for inducible regulation.","method":"Transcriptional start site mapping and promoter-reporter assays with tet operator integration in T. gondii","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct promoter functional assay with defined start site and quantitative repression measurement, single lab, two complementary approaches (start site mapping + operator integration)","pmids":["16516216"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"Conditional knockdown of rps13 (Δrps13) in T. gondii causes marked reduction of RPS13 protein expression, diminution of 18S rRNA, concomitant reduction of RPL22 protein (at a slower rate), cessation of parasite replication, and arrest of parasites in the G1 phase of the cell cycle, establishing RPS13 as required for ribosome biogenesis and cell-cycle progression through G1.","method":"Conditional knockdown via TetR/tetO system (Δrps13 parasites ± anhydrotetracycline), Western blot, quantitative RNA analysis, cell-cycle phase analysis","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional KO with defined phenotypic readouts (G1 arrest, 18S RNA loss, RPL22 destabilization) and rescue experiment, multiple orthogonal methods in a single rigorous study","pmids":["21124925"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"Depletion of RPS13 in T. gondii leads to persistence of parasites in vitro for months without proliferation, and this proliferation arrest phenotype can be rescued by addition of anhydrotetracycline (ATc), demonstrating that RPS13 depletion causes a reversible non-replicative persistence state in vitro.","method":"Long-term culture of Δrps13 parasites ± ATc with proliferation monitoring and rescue assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined conditional system with rescue, single lab, functional persistence phenotype established","pmids":["21124925"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"finding":"An Apetala2 (AP2) transcription factor domain within T. gondii ribosomal protein promoters (including the rps13 promoter region) binds nuclear extract proteins, as demonstrated by EMSA and ChIP, and these promoter domains appear to associate with histone acetyltransferases.","method":"Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal biochemical methods (EMSA + ChIP), single lab; association with histone acetyltransferases is indirect","pmids":["21124925"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"T. gondii RPS13 is a ribosomal small-subunit protein whose expression, driven by a promoter with a defined transcriptional start site regulated by AP2-family factors and histone acetyltransferases, is essential for 18S rRNA accumulation, ribosome biogenesis, and cell-cycle progression: its depletion arrests parasites in G1, destabilizes the large-subunit protein RPL22, halts proliferation, and induces a reversible non-replicative persistence state in vitro."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, RPS13 is a small-subunit ribosomal protein required for ribosome biogenesis and cell-cycle progression [PMID:21124925]. Conditional knockdown depletes RPS13 protein, reduces 18S rRNA, and secondarily destabilizes the large-subunit protein RPL22, arresting parasites in G1 and halting replication [PMID:21124925]; the resulting proliferation block persists for months in vitro yet is fully reversible upon restoring RPS13 expression, defining a non-replicative persistence state [PMID:21124925]. Its transcription is controlled by a promoter with a single defined start site [PMID:16516216] whose ribosomal-protein promoter domain contains an Apetala2 (AP2) transcription factor binding element that engages nuclear proteins and associates with histone acetyltransferases [PMID:21124925]. Beyond these findings, the biochemical role of RPS13 within the assembled ribosome has not been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Before this work the regulatory architecture of the rps13 gene was undefined; mapping the promoter established a single transcriptional start site and the operator placement needed to build an inducible knockdown system.","evidence":"Transcriptional start site mapping and promoter-reporter assays with tet operator integration in T. gondii","pmids":["16516216"],"confidence":"Medium","gaps":["The native transcription factors acting at the start site were not identified in this study","Repression was measured on a reporter, not the endogenous locus"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"claim":"Whether RPS13 is functionally required for parasite growth was unknown; conditional knockdown showed its loss collapses 18S rRNA levels, destabilizes RPL22, and arrests the cell cycle in G1, establishing RPS13 as essential for ribosome biogenesis and G1 progression.","evidence":"Conditional TetR/tetO knockdown ±anhydrotetracycline with Western blot, RNA quantification, and cell-cycle analysis","pmids":["21124925"],"confidence":"High","gaps":["Direct role of RPS13 in 40S subunit assembly versus indirect stabilization not resolved","Mechanism linking ribosome deficiency to G1 arrest not defined","Whether RPL22 loss is a direct or downstream consequence not distinguished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"claim":"It was unclear whether ribosomal protein depletion kills parasites or drives a dormant state; long-term culture with rescue showed RPS13-depleted parasites persist non-replicatively for months and resume growth when expression is restored, defining a reversible persistence phenotype.","evidence":"Long-term culture of Δrps13 parasites ±ATc with proliferation monitoring and rescue","pmids":["21124925"],"confidence":"Medium","gaps":["Molecular state of persistent parasites (bradyzoite-like markers, metabolic status) not characterized","Relevance to in vivo latency not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2010,"claim":"How ribosomal protein genes including rps13 are transcriptionally coordinated was open; EMSA and ChIP identified an AP2 domain binding element in the promoter and linked it to histone acetyltransferase activity, implicating AP2 factors and chromatin modification in their regulation.","evidence":"EMSA and ChIP on ribosomal protein promoter domains","pmids":["21124925"],"confidence":"Medium","gaps":["The specific AP2 factor binding the rps13 promoter was not identified","Association with histone acetyltransferases is indirect and not shown to act directly on rps13"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The structural role of RPS13 within the T. gondii 40S subunit, its rRNA and protein contacts, and the mechanistic link between its loss and reversible persistence remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or biochemical characterization of RPS13 in the assembled ribosome","Identity of the regulatory AP2 factor and its direct chromatin effects unresolved","Signaling pathway coupling ribosome deficiency to G1 arrest and persistence unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["40S small ribosomal subunit (inferred functional context)"],"partners":["RPL22 (DESTABILIZED UPON RPS13 DEPLETION)","AP2-DOMAIN TRANSCRIPTION FACTOR (PROMOTER BINDING)","HISTONE ACETYLTRANSFERASES (PROMOTER ASSOCIATION)"],"other_free_text":["RPS13 depletion reduces 18S rRNA accumulation and arrests parasites in G1 [#1].","RPS13 loss induces a reversible non-replicative persistence state rescuable by restoring expression [#2].","The rps13 promoter has a single transcriptional start site amenable to tet-based inducible control [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"16516216","id":"PMC_16516216","title":"Tight control of transcription in Toxoplasma gondii using an alternative tet repressor.","date":"2006","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/16516216","citation_count":24,"is_preprint":false},{"pmid":"21124925","id":"PMC_21124925","title":"T. gondii RP promoters & knockdown reveal molecular pathways associated with proliferation and cell-cycle arrest.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21124925","citation_count":22,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3615,"output_tokens":1156,"usd":0.014093,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6118,"output_tokens":2237,"usd":0.043257,"stage2_stop_reason":"end_turn"},"total_usd":0.05735,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"The T. gondii RPS13 promoter has a single major transcriptional start site, and integration of four tet operator elements 23–43 bp upstream of this start site results in maximal transcriptional repression (88-fold), establishing the promoter architecture required for inducible regulation.\",\n      \"method\": \"Transcriptional start site mapping and promoter-reporter assays with tet operator integration in T. gondii\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct promoter functional assay with defined start site and quantitative repression measurement, single lab, two complementary approaches (start site mapping + operator integration)\",\n      \"pmids\": [\"16516216\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Conditional knockdown of rps13 (Δrps13) in T. gondii causes marked reduction of RPS13 protein expression, diminution of 18S rRNA, concomitant reduction of RPL22 protein (at a slower rate), cessation of parasite replication, and arrest of parasites in the G1 phase of the cell cycle, establishing RPS13 as required for ribosome biogenesis and cell-cycle progression through G1.\",\n      \"method\": \"Conditional knockdown via TetR/tetO system (Δrps13 parasites ± anhydrotetracycline), Western blot, quantitative RNA analysis, cell-cycle phase analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional KO with defined phenotypic readouts (G1 arrest, 18S RNA loss, RPL22 destabilization) and rescue experiment, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"21124925\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Depletion of RPS13 in T. gondii leads to persistence of parasites in vitro for months without proliferation, and this proliferation arrest phenotype can be rescued by addition of anhydrotetracycline (ATc), demonstrating that RPS13 depletion causes a reversible non-replicative persistence state in vitro.\",\n      \"method\": \"Long-term culture of Δrps13 parasites ± ATc with proliferation monitoring and rescue assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined conditional system with rescue, single lab, functional persistence phenotype established\",\n      \"pmids\": [\"21124925\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"An Apetala2 (AP2) transcription factor domain within T. gondii ribosomal protein promoters (including the rps13 promoter region) binds nuclear extract proteins, as demonstrated by EMSA and ChIP, and these promoter domains appear to associate with histone acetyltransferases.\",\n      \"method\": \"Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal biochemical methods (EMSA + ChIP), single lab; association with histone acetyltransferases is indirect\",\n      \"pmids\": [\"21124925\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"T. gondii RPS13 is a ribosomal small-subunit protein whose expression, driven by a promoter with a defined transcriptional start site regulated by AP2-family factors and histone acetyltransferases, is essential for 18S rRNA accumulation, ribosome biogenesis, and cell-cycle progression: its depletion arrests parasites in G1, destabilizes the large-subunit protein RPL22, halts proliferation, and induces a reversible non-replicative persistence state in vitro.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, RPS13 is a small-subunit ribosomal protein required for ribosome biogenesis and cell-cycle progression [#1]. Conditional knockdown depletes RPS13 protein, reduces 18S rRNA, and secondarily destabilizes the large-subunit protein RPL22, arresting parasites in G1 and halting replication [#1]; the resulting proliferation block persists for months in vitro yet is fully reversible upon restoring RPS13 expression, defining a non-replicative persistence state [#2]. Its transcription is controlled by a promoter with a single defined start site [#0] whose ribosomal-protein promoter domain contains an Apetala2 (AP2) transcription factor binding element that engages nuclear proteins and associates with histone acetyltransferases [#3]. Beyond these findings, the biochemical role of RPS13 within the assembled ribosome has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Before this work the regulatory architecture of the rps13 gene was undefined; mapping the promoter established a single transcriptional start site and the operator placement needed to build an inducible knockdown system.\",\n      \"evidence\": \"Transcriptional start site mapping and promoter-reporter assays with tet operator integration in T. gondii\",\n      \"pmids\": [\"16516216\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The native transcription factors acting at the start site were not identified in this study\",\n        \"Repression was measured on a reporter, not the endogenous locus\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether RPS13 is functionally required for parasite growth was unknown; conditional knockdown showed its loss collapses 18S rRNA levels, destabilizes RPL22, and arrests the cell cycle in G1, establishing RPS13 as essential for ribosome biogenesis and G1 progression.\",\n      \"evidence\": \"Conditional TetR/tetO knockdown ±anhydrotetracycline with Western blot, RNA quantification, and cell-cycle analysis\",\n      \"pmids\": [\"21124925\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct role of RPS13 in 40S subunit assembly versus indirect stabilization not resolved\",\n        \"Mechanism linking ribosome deficiency to G1 arrest not defined\",\n        \"Whether RPL22 loss is a direct or downstream consequence not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"It was unclear whether ribosomal protein depletion kills parasites or drives a dormant state; long-term culture with rescue showed RPS13-depleted parasites persist non-replicatively for months and resume growth when expression is restored, defining a reversible persistence phenotype.\",\n      \"evidence\": \"Long-term culture of Δrps13 parasites ±ATc with proliferation monitoring and rescue\",\n      \"pmids\": [\"21124925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular state of persistent parasites (bradyzoite-like markers, metabolic status) not characterized\",\n        \"Relevance to in vivo latency not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"How ribosomal protein genes including rps13 are transcriptionally coordinated was open; EMSA and ChIP identified an AP2 domain binding element in the promoter and linked it to histone acetyltransferase activity, implicating AP2 factors and chromatin modification in their regulation.\",\n      \"evidence\": \"EMSA and ChIP on ribosomal protein promoter domains\",\n      \"pmids\": [\"21124925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific AP2 factor binding the rps13 promoter was not identified\",\n        \"Association with histone acetyltransferases is indirect and not shown to act directly on rps13\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural role of RPS13 within the T. gondii 40S subunit, its rRNA and protein contacts, and the mechanistic link between its loss and reversible persistence remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or biochemical characterization of RPS13 in the assembled ribosome\",\n        \"Identity of the regulatory AP2 factor and its direct chromatin effects unresolved\",\n        \"Signaling pathway coupling ribosome deficiency to G1 arrest and persistence unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042254\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000082\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"40S small ribosomal subunit (inferred functional context)\"],\n    \"partners\": [\"RPL22 (destabilized upon RPS13 depletion)\", \"AP2-domain transcription factor (promoter binding)\", \"histone acetyltransferases (promoter association)\"],\n    \"other_free_text\": [\n      \"RPS13 depletion reduces 18S rRNA accumulation and arrests parasites in G1 [#1].\",\n      \"RPS13 loss induces a reversible non-replicative persistence state rescuable by restoring expression [#2].\",\n      \"The rps13 promoter has a single transcriptional start site amenable to tet-based inducible control [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_270380","name":"RPS13","product":"ribosomal protein RPS13","uniprot_acc":"A0A125YSG4","chromosome":"TGME49_chrVIII","start_pos":5240564},{"strain":"GT1","gene_id":"TGGT1_270380","name":null,"product":"ribosomal protein RPS13","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":5238468},{"strain":"RH88","gene_id":"TGRH88_080990","name":null,"product":"ribosomal protein RPS13","uniprot_acc":null,"chromosome":"CM023089","start_pos":10359072},{"strain":"VEG","gene_id":"TGVEG_270380","name":null,"product":"ribosomal protein RPS13","uniprot_acc":"A0A125YSG6","chromosome":"TGVEG_chrVIII","start_pos":5253872}]}