{"gene":"PF3D7_1126800","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2019,"finding":"Disruption of PbSR-MG (the P. berghei ortholog of PF3D7_1126800/SR-MG) perturbs sex-specific alternative splicing and decreases the ability of parasites to differentiate into male gametes and oocysts, thereby reducing transmission between vertebrate and insect hosts.","method":"RNA-seq to compare splicing across life-cycle stages combined with genetic disruption (knockout) of PbSR-MG in P. berghei, with phenotypic readout of male gametogenesis and oocyst formation","journal":"Genome biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotype (male gametogenesis and transmission defect) plus genome-wide splicing analysis; single lab but two orthogonal methods (RNA-seq + reverse genetics)","pmids":["31370870"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"PfSR-MG (PF3D7_1126800) transcript expression was downregulated in Pfsrpk1-knockout P. falciparum stage V gametocytes, placing SR-MG downstream of the SR-protein kinase PfSRPK1 in gametocyte gene regulation; PfSR-MG was the only splicing factor found to be downregulated in this context.","method":"Bulk RNA-seq comparison of wild-type PfNF54 and Pfsrpk1-knockout stage V gametocytes; differential gene expression analysis","journal":"Microbiology spectrum","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptomic observation from a single lab in the context of a different gene's knockout; no direct functional experiment on SR-MG itself","pmids":["36094218"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]}],"current_model":"SR-MG (PF3D7_1126800) is an alternative splicing factor whose disruption in P. berghei perturbs sex-specific pre-mRNA splicing, impairs male gametogenesis and oocyst formation, and reduces mosquito transmission; in P. falciparum its transcript is regulated downstream of the SR-protein kinase PfSRPK1 in stage V gametocytes, but no direct functional experiment in P. falciparum has yet defined its molecular mechanism."},"narrative":{"mechanistic_narrative":"SR-MG (PF3D7_1126800) is an alternative splicing factor that regulates sex-specific pre-mRNA splicing during Plasmodium sexual differentiation and transmission. In P. berghei, genetic disruption of the ortholog PbSR-MG perturbs sex-specific alternative splicing and impairs the parasite's ability to differentiate into male gametes and to form oocysts, thereby reducing transmission between vertebrate and insect hosts [PMID:31370870]. In P. falciparum, the PfSR-MG transcript is downregulated in Pfsrpk1-knockout stage V gametocytes—and was the only splicing factor so affected—placing SR-MG downstream of the SR-protein kinase PfSRPK1 in gametocyte gene regulation [PMID:36094218]. No direct functional experiment on SR-MG itself has been performed in P. falciparum, so its molecular mechanism in this species remains uncharacterized in the available corpus.","teleology":[{"year":2019,"claim":"Established that SR-MG functions as a sex-specific alternative splicing regulator required for parasite transmission, defining the gene's cellular role rather than leaving it a putative splicing factor.","evidence":"Genetic knockout of the P. berghei ortholog PbSR-MG combined with life-cycle-stage RNA-seq and phenotypic readout of male gametogenesis and oocyst formation","pmids":["31370870"],"confidence":"Medium","gaps":["The direct RNA substrates and splice sites regulated by SR-MG are not defined","Molecular mechanism of splice-site selection or spliceosome interaction is untested","Findings are in P. berghei; direct loss-of-function in P. falciparum is absent"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"Placed SR-MG within a gametocyte gene-regulatory hierarchy by showing its transcript depends on the SR-protein kinase PfSRPK1, but this was a correlative transcriptomic observation, not a functional test of SR-MG.","evidence":"Bulk RNA-seq of wild-type PfNF54 versus Pfsrpk1-knockout P. falciparum stage V gametocytes with differential expression analysis","pmids":["36094218"],"confidence":"Low","gaps":["Transcriptomic association only; no direct functional experiment on SR-MG and no evidence of direct regulation versus indirect downstream effect","Whether SR-MG protein activity or its own splicing targets change in this context is unknown","No demonstration that PfSRPK1 phosphorylates or physically acts on SR-MG"],"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]},{"year":null,"claim":"The direct molecular mechanism of SR-MG in P. falciparum—its RNA targets, spliceosome partners, and the biochemical consequence of its regulation by PfSRPK1—remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct loss-of-function or biochemical experiment on SR-MG in P. falciparum","No identified RNA substrates or interacting spliceosomal components","No structural or domain-level characterization in the corpus"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFSRPK1 (SR-PROTEIN KINASE; SR-MG TRANSCRIPT DOWNREGULATED IN PFSRPK1-KNOCKOUT STAGE V GAMETOCYTES) [#1]"],"other_free_text":["Disruption of the P. berghei ortholog PbSR-MG perturbs sex-specific alternative splicing and impairs male gametogenesis, oocyst formation, and mosquito transmission [#0]","In P. falciparum, PfSR-MG transcript was the only splicing factor downregulated in Pfsrpk1-knockout stage V gametocytes, placing it downstream of PfSRPK1 in gametocyte gene regulation [#1]","No direct functional experiment has defined the molecular mechanism of SR-MG in P. falciparum"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"31370870","id":"PMC_31370870","title":"Alternative splicing is required for stage differentiation in malaria parasites.","date":"2019","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/31370870","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42272758","id":"","title":"The serine-arginine-rich protein PfSR-X2 modulates human malaria parasite gene expression during the intraerythrocytic developmental cycle.","date":"2026","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42272758","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SR-MG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36094218","id":"","title":"PfSRPK1 Regulates Asexual Blood Stage Schizogony and Is Essential for Male Gamete Formation.","date":"2022","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/36094218","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SR-MG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38824128","id":"","title":"An axonemal intron splicing program sustains Plasmodium male development.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38824128","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SR-MG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32019802","id":"","title":"RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver Infection.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32019802","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SR-MG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7603,"output_tokens":716,"usd":0.016775,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5348,"output_tokens":1703,"usd":0.034658,"stage2_stop_reason":"end_turn"},"total_usd":0.051433,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"Disruption of PbSR-MG (the P. berghei ortholog of PF3D7_1126800/SR-MG) perturbs sex-specific alternative splicing and decreases the ability of parasites to differentiate into male gametes and oocysts, thereby reducing transmission between vertebrate and insect hosts.\",\n      \"method\": \"RNA-seq to compare splicing across life-cycle stages combined with genetic disruption (knockout) of PbSR-MG in P. berghei, with phenotypic readout of male gametogenesis and oocyst formation\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotype (male gametogenesis and transmission defect) plus genome-wide splicing analysis; single lab but two orthogonal methods (RNA-seq + reverse genetics)\",\n      \"pmids\": [\"31370870\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PfSR-MG (PF3D7_1126800) transcript expression was downregulated in Pfsrpk1-knockout P. falciparum stage V gametocytes, placing SR-MG downstream of the SR-protein kinase PfSRPK1 in gametocyte gene regulation; PfSR-MG was the only splicing factor found to be downregulated in this context.\",\n      \"method\": \"Bulk RNA-seq comparison of wild-type PfNF54 and Pfsrpk1-knockout stage V gametocytes; differential gene expression analysis\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptomic observation from a single lab in the context of a different gene's knockout; no direct functional experiment on SR-MG itself\",\n      \"pmids\": [\"36094218\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SR-MG (PF3D7_1126800) is an alternative splicing factor whose disruption in P. berghei perturbs sex-specific pre-mRNA splicing, impairs male gametogenesis and oocyst formation, and reduces mosquito transmission; in P. falciparum its transcript is regulated downstream of the SR-protein kinase PfSRPK1 in stage V gametocytes, but no direct functional experiment in P. falciparum has yet defined its molecular mechanism.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SR-MG (PF3D7_1126800) is an alternative splicing factor that regulates sex-specific pre-mRNA splicing during Plasmodium sexual differentiation and transmission. In P. berghei, genetic disruption of the ortholog PbSR-MG perturbs sex-specific alternative splicing and impairs the parasite's ability to differentiate into male gametes and to form oocysts, thereby reducing transmission between vertebrate and insect hosts [#0]. In P. falciparum, the PfSR-MG transcript is downregulated in Pfsrpk1-knockout stage V gametocytes—and was the only splicing factor so affected—placing SR-MG downstream of the SR-protein kinase PfSRPK1 in gametocyte gene regulation [#1]. No direct functional experiment on SR-MG itself has been performed in P. falciparum, so its molecular mechanism in this species remains uncharacterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established that SR-MG functions as a sex-specific alternative splicing regulator required for parasite transmission, defining the gene's cellular role rather than leaving it a putative splicing factor.\",\n      \"evidence\": \"Genetic knockout of the P. berghei ortholog PbSR-MG combined with life-cycle-stage RNA-seq and phenotypic readout of male gametogenesis and oocyst formation\",\n      \"pmids\": [\n        \"31370870\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The direct RNA substrates and splice sites regulated by SR-MG are not defined\",\n        \"Molecular mechanism of splice-site selection or spliceosome interaction is untested\",\n        \"Findings are in P. berghei; direct loss-of-function in P. falciparum is absent\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed SR-MG within a gametocyte gene-regulatory hierarchy by showing its transcript depends on the SR-protein kinase PfSRPK1, but this was a correlative transcriptomic observation, not a functional test of SR-MG.\",\n      \"evidence\": \"Bulk RNA-seq of wild-type PfNF54 versus Pfsrpk1-knockout P. falciparum stage V gametocytes with differential expression analysis\",\n      \"pmids\": [\n        \"36094218\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcriptomic association only; no direct functional experiment on SR-MG and no evidence of direct regulation versus indirect downstream effect\",\n        \"Whether SR-MG protein activity or its own splicing targets change in this context is unknown\",\n        \"No demonstration that PfSRPK1 phosphorylates or physically acts on SR-MG\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"NF54\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular mechanism of SR-MG in P. falciparum—its RNA targets, spliceosome partners, and the biochemical consequence of its regulation by PfSRPK1—remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct loss-of-function or biochemical experiment on SR-MG in P. falciparum\",\n        \"No identified RNA substrates or interacting spliceosomal components\",\n        \"No structural or domain-level characterization in the corpus\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0008380\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0000380\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfSRPK1 (SR-protein kinase; SR-MG transcript downregulated in Pfsrpk1-knockout stage V gametocytes) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"Disruption of the P. berghei ortholog PbSR-MG perturbs sex-specific alternative splicing and impairs male gametogenesis, oocyst formation, and mosquito transmission [#0]\",\n      \"In P. falciparum, PfSR-MG transcript was the only splicing factor downregulated in Pfsrpk1-knockout stage V gametocytes, placing it downstream of PfSRPK1 in gametocyte gene regulation [#1]\",\n      \"No direct functional experiment has defined the molecular mechanism of SR-MG in P. falciparum\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1126800","name":null,"product":"alternative splicing factor SR-MG, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0921600","name":null,"product":"alternative splicing factor SR-MG","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0924800","name":null,"product":"alternative splicing factor SR-MG, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SR-MG","evaluation":null}