{"gene":"TG_219520","gene_symbol":"PRMT1","run_date":"2026-09-08T11:06:35","timeline":{"discoveries":[{"year":2012,"finding":"TgPRMT1 methylates the N-terminal RGG-repeat domain of the single Toxoplasma gondii Argonaute (TgAgo), and this methylation is required for recruitment of Tudor staphylococcal nuclease (TSN) to the Ago complex, enabling Ca2+-dependent, imperfectly paired guide RNA-directed target RNA cleavage.","method":"Co-immunoprecipitation of TgAgo complex; mutational analysis of RGG-repeat domain; in vitro RNA cleavage assays (Mg2+- and Ca2+-dependence); PRMT1 knockout parasites showing loss of TSN recruitment and abnormal growth; chemical inhibition of Arg-methylation","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, mutagenesis of substrate domain, in vitro activity assays, and genetic knockout with specific phenotypic readout, all in a single study","pmids":["22309152"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"finding":"TgPRMT1 localizes primarily in the cytoplasm with enrichment at the pericentriolar material; deletion of PRMT1 (Δprmt1) causes defects in centrosome segregation, abnormal daughter buds, perturbed centrosome stoichiometry, loss of synchronous replication, and slow growth during tachyzoite endodyogeny — phenotypes rescued by PRMT1mRFP complementation.","method":"Genetic deletion of PRMT1 (Δprmt1 strain); fluorescence localization of tagged PRMT1mRFP; complementation rescue; whole-genome expression profiling; microscopic analysis of centrosome stoichiometry and daughter-bud morphology","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with complementation rescue, direct localization by live imaging, and multiple orthogonal phenotypic readouts in a single rigorous study","pmids":["26838719"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"Comparative monomethylarginine proteomics using anti-MMA affinity purification and mass spectrometry identified numerous putative PRMT1 substrates in T. gondii, including RNA-binding proteins, ApiAP2 transcription factors, and kinases, establishing PRMT1 as the major contributor to arginine monomethylation in this organism; 90% of MMA-modified proteins were also phosphorylated, suggesting crosstalk between MMA and phosphorylation.","method":"Anti-MMA antibody affinity purification followed by mass spectrometry; comparative proteomics between wild-type and PRMT1-depleted parasites","journal":"Molecular & cellular proteomics : MCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry-based comparative proteomics with affinity purification, single lab, substrate-level identification without in vitro reconstitution of methyltransferase activity","pmids":["28143887"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgPRMT1 is a cytoplasmic arginine methyltransferase enriched at the pericentriolar material that (1) methylates the RGG-repeat domain of TgAgo to recruit Tudor staphylococcal nuclease into the RNA silencing complex, enabling target RNA cleavage, and (2) is essential for accurate centrosome segregation and synchronous endodyogeny, with its broader substrate repertoire including RNA-binding proteins, ApiAP2 transcription factors, and kinases constituting the majority of the T. gondii monomethylarginine proteome."},"narrative":{"mechanistic_narrative":"PRMT1 in Toxoplasma gondii is a cytoplasmic arginine methyltransferase that governs both RNA silencing and cell-division fidelity, and it constitutes the major contributor to arginine monomethylation in this organism [PMID:28143887]. In the RNA silencing pathway, TgPRMT1 methylates the N-terminal RGG-repeat domain of the single Argonaute protein TgAgo, and this modification is required to recruit Tudor staphylococcal nuclease into the Ago complex, enabling Ca2+-dependent, guide RNA-directed target RNA cleavage [PMID:22309152]. Independently, TgPRMT1 is enriched at the pericentriolar material and is essential for accurate centrosome segregation and synchronous endodyogeny: its deletion perturbs centrosome stoichiometry, produces abnormal daughter buds, and slows tachyzoite growth, defects reversed by complementation [PMID:26838719]. Its broader substrate repertoire spans RNA-binding proteins, ApiAP2 transcription factors, and kinases, with a strong overlap between monomethylarginine and phosphorylation marks pointing to crosstalk between the two modifications [PMID:28143887].","teleology":[{"year":2012,"claim":"It was unknown how the Toxoplasma RNA silencing machinery assembles its effector nuclease; this work established that PRMT1-catalyzed methylation of the TgAgo RGG domain is the molecular switch that recruits Tudor staphylococcal nuclease and licenses target RNA cleavage.","evidence":"reciprocal Co-IP of the TgAgo complex, RGG-domain mutagenesis, in vitro RNA cleavage assays, and PRMT1 knockout showing loss of TSN recruitment","pmids":["22309152"],"confidence":"High","gaps":["the biological RNA targets and physiological role of the cleavage activity are not defined","direct in vitro reconstitution of PRMT1 methyltransferase activity on TgAgo not shown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"claim":"Whether PRMT1 has functions beyond RNA silencing was unresolved; genetic deletion revealed an essential role in centrosome segregation and synchronous endodyogeny, localizing the enzyme to the pericentriolar material.","evidence":"Δprmt1 knockout with PRMT1mRFP complementation rescue, live-imaging localization, and microscopic analysis of centrosome stoichiometry and daughter-bud morphology","pmids":["26838719"],"confidence":"High","gaps":["the pericentriolar substrate(s) whose methylation drives centrosome fidelity are not identified","mechanistic link between methyltransferase activity and centrosome segregation not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"The full substrate scope of PRMT1 was unknown; comparative monomethylarginine proteomics established it as the major arginine monomethyltransferase in T. gondii and identified candidate substrates linking methylation to transcription, RNA metabolism, and signaling.","evidence":"anti-MMA affinity purification with mass spectrometry comparing wild-type and PRMT1-depleted parasites","pmids":["28143887"],"confidence":"Medium","gaps":["substrates identified by proteomics without in vitro reconstitution of direct methylation","functional consequence of the MMA-phosphorylation crosstalk not tested","which candidates are direct versus indirect PRMT1 targets not distinguished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How PRMT1 activity is coordinated between its RNA-silencing and centrosome roles, and which specific methylation events drive division fidelity, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no structural model of TgPRMT1 or its substrate recognition","regulation of PRMT1 activity and localization not characterized","direct causal link between individual substrate methylation and each phenotype not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TgAgo (Argonaute) RNA silencing complex, joined by Tudor staphylococcal nuclease upon PRMT1 methylation"],"partners":["TGAGO (ARGONAUTE)","TUDOR STAPHYLOCOCCAL NUCLEASE (TSN)","RNA-BINDING PROTEINS (CANDIDATE SUBSTRATES)","APIAP2 TRANSCRIPTION FACTORS (CANDIDATE SUBSTRATES)","KINASES (CANDIDATE SUBSTRATES)"],"other_free_text":["PRMT1 is the major contributor to arginine monomethylation in T. gondii; ~90% of MMA-modified proteins are also phosphorylated, indicating potential MMA-phosphorylation crosstalk [#2].","Δprmt1 phenotypes (centrosome segregation defects, abnormal daughter buds, loss of synchronous replication, slow growth) are rescued by PRMT1mRFP complementation [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"22309152","id":"PMC_22309152","title":"PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage by antisense guide RNA.","date":"2012","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22309152","citation_count":30,"is_preprint":false},{"pmid":"28143887","id":"PMC_28143887","title":"Comparative Monomethylarginine Proteomics Suggests that Protein Arginine Methyltransferase 1 (PRMT1) is a Significant Contributor to Arginine Monomethylation in Toxoplasma gondii.","date":"2017","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/28143887","citation_count":20,"is_preprint":false},{"pmid":"26838719","id":"PMC_26838719","title":"Toxoplasma gondii Arginine Methyltransferase 1 (PRMT1) Is Necessary for Centrosome Dynamics during Tachyzoite Cell Division.","date":"2016","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/26838719","citation_count":19,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4165,"output_tokens":1099,"usd":0.01449,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6034,"output_tokens":2398,"usd":0.04506,"stage2_stop_reason":"end_turn"},"total_usd":0.05955,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"TgPRMT1 methylates the N-terminal RGG-repeat domain of the single Toxoplasma gondii Argonaute (TgAgo), and this methylation is required for recruitment of Tudor staphylococcal nuclease (TSN) to the Ago complex, enabling Ca2+-dependent, imperfectly paired guide RNA-directed target RNA cleavage.\",\n      \"method\": \"Co-immunoprecipitation of TgAgo complex; mutational analysis of RGG-repeat domain; in vitro RNA cleavage assays (Mg2+- and Ca2+-dependence); PRMT1 knockout parasites showing loss of TSN recruitment and abnormal growth; chemical inhibition of Arg-methylation\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, mutagenesis of substrate domain, in vitro activity assays, and genetic knockout with specific phenotypic readout, all in a single study\",\n      \"pmids\": [\"22309152\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TgPRMT1 localizes primarily in the cytoplasm with enrichment at the pericentriolar material; deletion of PRMT1 (Δprmt1) causes defects in centrosome segregation, abnormal daughter buds, perturbed centrosome stoichiometry, loss of synchronous replication, and slow growth during tachyzoite endodyogeny — phenotypes rescued by PRMT1mRFP complementation.\",\n      \"method\": \"Genetic deletion of PRMT1 (Δprmt1 strain); fluorescence localization of tagged PRMT1mRFP; complementation rescue; whole-genome expression profiling; microscopic analysis of centrosome stoichiometry and daughter-bud morphology\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with complementation rescue, direct localization by live imaging, and multiple orthogonal phenotypic readouts in a single rigorous study\",\n      \"pmids\": [\"26838719\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Comparative monomethylarginine proteomics using anti-MMA affinity purification and mass spectrometry identified numerous putative PRMT1 substrates in T. gondii, including RNA-binding proteins, ApiAP2 transcription factors, and kinases, establishing PRMT1 as the major contributor to arginine monomethylation in this organism; 90% of MMA-modified proteins were also phosphorylated, suggesting crosstalk between MMA and phosphorylation.\",\n      \"method\": \"Anti-MMA antibody affinity purification followed by mass spectrometry; comparative proteomics between wild-type and PRMT1-depleted parasites\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry-based comparative proteomics with affinity purification, single lab, substrate-level identification without in vitro reconstitution of methyltransferase activity\",\n      \"pmids\": [\"28143887\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgPRMT1 is a cytoplasmic arginine methyltransferase enriched at the pericentriolar material that (1) methylates the RGG-repeat domain of TgAgo to recruit Tudor staphylococcal nuclease into the RNA silencing complex, enabling target RNA cleavage, and (2) is essential for accurate centrosome segregation and synchronous endodyogeny, with its broader substrate repertoire including RNA-binding proteins, ApiAP2 transcription factors, and kinases constituting the majority of the T. gondii monomethylarginine proteome.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PRMT1 in Toxoplasma gondii is a cytoplasmic arginine methyltransferase that governs both RNA silencing and cell-division fidelity, and it constitutes the major contributor to arginine monomethylation in this organism [#2]. In the RNA silencing pathway, TgPRMT1 methylates the N-terminal RGG-repeat domain of the single Argonaute protein TgAgo, and this modification is required to recruit Tudor staphylococcal nuclease into the Ago complex, enabling Ca2+-dependent, guide RNA-directed target RNA cleavage [#0]. Independently, TgPRMT1 is enriched at the pericentriolar material and is essential for accurate centrosome segregation and synchronous endodyogeny: its deletion perturbs centrosome stoichiometry, produces abnormal daughter buds, and slows tachyzoite growth, defects reversed by complementation [#1]. Its broader substrate repertoire spans RNA-binding proteins, ApiAP2 transcription factors, and kinases, with a strong overlap between monomethylarginine and phosphorylation marks pointing to crosstalk between the two modifications [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"It was unknown how the Toxoplasma RNA silencing machinery assembles its effector nuclease; this work established that PRMT1-catalyzed methylation of the TgAgo RGG domain is the molecular switch that recruits Tudor staphylococcal nuclease and licenses target RNA cleavage.\",\n      \"evidence\": \"reciprocal Co-IP of the TgAgo complex, RGG-domain mutagenesis, in vitro RNA cleavage assays, and PRMT1 knockout showing loss of TSN recruitment\",\n      \"pmids\": [\"22309152\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"the biological RNA targets and physiological role of the cleavage activity are not defined\",\n        \"direct in vitro reconstitution of PRMT1 methyltransferase activity on TgAgo not shown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether PRMT1 has functions beyond RNA silencing was unresolved; genetic deletion revealed an essential role in centrosome segregation and synchronous endodyogeny, localizing the enzyme to the pericentriolar material.\",\n      \"evidence\": \"Δprmt1 knockout with PRMT1mRFP complementation rescue, live-imaging localization, and microscopic analysis of centrosome stoichiometry and daughter-bud morphology\",\n      \"pmids\": [\"26838719\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"the pericentriolar substrate(s) whose methylation drives centrosome fidelity are not identified\",\n        \"mechanistic link between methyltransferase activity and centrosome segregation not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The full substrate scope of PRMT1 was unknown; comparative monomethylarginine proteomics established it as the major arginine monomethyltransferase in T. gondii and identified candidate substrates linking methylation to transcription, RNA metabolism, and signaling.\",\n      \"evidence\": \"anti-MMA affinity purification with mass spectrometry comparing wild-type and PRMT1-depleted parasites\",\n      \"pmids\": [\"28143887\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"substrates identified by proteomics without in vitro reconstitution of direct methylation\",\n        \"functional consequence of the MMA-phosphorylation crosstalk not tested\",\n        \"which candidates are direct versus indirect PRMT1 targets not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PRMT1 activity is coordinated between its RNA-silencing and centrosome roles, and which specific methylation events drive division fidelity, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no structural model of TgPRMT1 or its substrate recognition\",\n        \"regulation of PRMT1 activity and localization not characterized\",\n        \"direct causal link between individual substrate methylation and each phenotype not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008276\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0035242\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000242\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016246\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0007098\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"TgAgo (Argonaute) RNA silencing complex, joined by Tudor staphylococcal nuclease upon PRMT1 methylation\"\n    ],\n    \"partners\": [\n      \"TgAgo (Argonaute)\",\n      \"Tudor staphylococcal nuclease (TSN)\",\n      \"RNA-binding proteins (candidate substrates)\",\n      \"ApiAP2 transcription factors (candidate substrates)\",\n      \"kinases (candidate substrates)\"\n    ],\n    \"other_free_text\": [\n      \"PRMT1 is the major contributor to arginine monomethylation in T. gondii; ~90% of MMA-modified proteins are also phosphorylated, indicating potential MMA-phosphorylation crosstalk [#2].\",\n      \"Δprmt1 phenotypes (centrosome segregation defects, abnormal daughter buds, loss of synchronous replication, slow growth) are rescued by PRMT1mRFP complementation [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_219520","name":"PRMT1","product":"histone arginine methyltransferase PRMT1","uniprot_acc":"A0A125YYW8","chromosome":"TGME49_chrXII","start_pos":885564},{"strain":"GT1","gene_id":"TGGT1_219520","name":null,"product":"histone arginine methyltransferase PRMT1","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":823809},{"strain":"RH88","gene_id":"TGRH88_058120","name":null,"product":"histone arginine methyltransferase PRMT1","uniprot_acc":null,"chromosome":"CM023093","start_pos":896561},{"strain":"VEG","gene_id":"TGVEG_219520","name":null,"product":"histone arginine methyltransferase PRMT1","uniprot_acc":"B9QLS1","chromosome":"TGVEG_chrXII","start_pos":858267}]}