{"gene":"PF3D7_1103800","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2024,"finding":"In P. yoelii female gametocytes, DOZI (DDX6 orthologue) interacts with NOT1-G (PF3D7_1103800 orthologue), and upon fertilization (zygote stage) this interaction is replaced by an interaction between DOZI and the canonical NOT1, providing a mechanistic model for how mRNAs are released from translational repression during the host-to-vector transmission event.","method":"TurboID-based proximity proteomics across female gametocyte and zygote stages, cross-validated by ultrastructure expansion microscopy and structured illumination microscopy","journal":"bioRxiv : the preprint server for biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — proximity proteomics with microscopy cross-validation in a single lab; preprint, not yet peer-reviewed at time of this entry","pmids":["38352447"],"is_preprint":true,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"finding":"In P. yoelii female gametocytes, DOZI exchanges its interaction from NOT1-G (PF3D7_1103800 orthologue) to the canonical NOT1 in zygotes, as determined by TurboID-based proximity proteomics; this compositional switch in the DOZI/CITH/ALBA complex is consistent with a trigger for the release of mRNAs from translational repression upon fertilization.","method":"TurboID-based proximity proteomics (DIA-MS) comparing female gametocytes and zygotes; supported by comparative transcriptomics and proteomics","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity proteomics with quantitative DIA-MS in peer-reviewed publication, single lab but two orthogonal approaches (proximity proteomics + microscopy)","pmids":["39777415"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2015,"finding":"NOT1-G (PF3D7_1103800) was identified bioinformatically as a component of the PfCaf1-CCR4-NOT complex in P. falciparum through comparative interactome analysis using human and Plasmodium protein-protein interaction datasets.","method":"Bioinformatic/comparative interactome analysis; protein-protein interaction network construction using Cytoscape","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of NOT1-G specifically","pmids":["26525978"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"NOT1-G (PF3D7_1103800) is a subunit of the CAF1/CCR4/NOT complex in Plasmodium that associates with DOZI in female gametocytes to maintain translational repression of specific mRNAs; upon fertilization, DOZI exchanges NOT1-G for the canonical NOT1 in zygotes, providing a mechanistic switch for the global release of translational repression during host-to-vector transmission."},"narrative":{"mechanistic_narrative":"NOT1-G (PF3D7_1103800) is a Plasmodium-specific scaffold subunit associated with the CAF1/CCR4/NOT complex that functions in the stage-specific control of translational repression during malaria parasite transmission [PMID:38352447, PMID:39777415]. In P. yoelii female gametocytes, NOT1-G engages the DDX6-family helicase DOZI, and this interaction is a defining feature of the repressed state; upon fertilization, DOZI exchanges NOT1-G for the canonical NOT1 in the zygote, a compositional switch within the DOZI/CITH/ALBA complex that provides a mechanistic trigger for the global release of stored mRNAs from translational repression during the host-to-vector transition [PMID:38352447, PMID:39777415]. Its membership in the PfCaf1-CCR4-NOT complex was first predicted bioinformatically in P. falciparum [PMID:26525978]. Beyond this DOZI-dependent scaffold role in transmission-stage translational control, no direct enzymatic activity, substrate mRNA repertoire, or structural detail for NOT1-G has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Before any functional work, it was unknown whether NOT1-G belonged to the parasite CCR4-NOT machinery at all; comparative interactome analysis placed it within the PfCaf1-CCR4-NOT complex, establishing a candidate role in mRNA regulation.","evidence":"Bioinformatic comparative interactome analysis and protein-protein interaction network construction in P. falciparum","pmids":["26525978"],"confidence":"Low","gaps":["Computational prediction only, with no direct experimental validation of NOT1-G specifically","No demonstration of physical interaction or subcellular context","No stage-specific or functional assignment"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"It was unknown how repressed maternal mRNAs are released from translational silencing at fertilization; proximity proteomics showed DOZI interacts with NOT1-G in female gametocytes and swaps to canonical NOT1 in zygotes, providing a compositional-switch model for derepression during transmission.","evidence":"TurboID proximity proteomics across gametocyte and zygote stages, cross-validated by expansion and structured illumination microscopy in P. yoelii (preprint)","pmids":["38352447"],"confidence":"Medium","gaps":["Preprint form at time of entry; proximity proteomics infers association, not direct binding","Does not identify which mRNAs are controlled by the NOT1-G-containing complex","Mechanism driving the NOT1-G-to-NOT1 exchange is not defined"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"claim":"The gametocyte-to-zygote exchange model was extended and quantified, confirming that DOZI shifts from NOT1-G to canonical NOT1 as part of a remodeling of the DOZI/CITH/ALBA complex consistent with a fertilization-triggered release of translational repression.","evidence":"TurboID proximity proteomics with quantitative DIA-MS comparing female gametocytes and zygotes, supported by comparative transcriptomics and proteomics in P. yoelii","pmids":["39777415"],"confidence":"Medium","gaps":["Single-lab study relying on proximity labeling rather than direct structural/biochemical reconstitution","Functional consequence of removing NOT1-G on mRNA derepression not directly tested","Structural basis for DOZI selecting NOT1-G versus NOT1 unresolved"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"The direct molecular activity of NOT1-G, its specific mRNA targets, and the structural basis for its stage-specific exchange with canonical NOT1 remain undetermined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined biochemical or scaffolding activity for NOT1-G in isolation","No identified repressed transcript repertoire dependent on NOT1-G","No structural model of the DOZI–NOT1-G interaction or the exchange mechanism"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CAF1/CCR4/NOT (PfCaf1-CCR4-NOT) complex","DOZI/CITH/ALBA translational repression complex"],"partners":["DOZI (DDX6 ORTHOLOGUE)","CANONICAL NOT1"],"other_free_text":["Findings on the DOZI–NOT1-G interaction and its gametocyte-to-zygote exchange derive from P. yoelii; the original complex-membership assignment derives from P. falciparum bioinformatics.","Proposed to act as a stage-specific scaffold whose replacement by canonical NOT1 at fertilization triggers release of maternal mRNAs from translational repression during host-to-vector transmission."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26525978","id":"PMC_26525978","title":"A bioinformatic survey of RNA-binding proteins in Plasmodium.","date":"2015","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/26525978","citation_count":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21803864","id":"PMC_21803864","title":"CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins.","date":"2011","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/21803864","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30703164","id":"PMC_30703164","title":"Plasmodium male gametocyte development and transmission are critically regulated by the two putative deadenylases of the CAF1/CCR4/NOT complex.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/30703164","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4","NOT","PyCCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31531994","id":"PMC_31531994","title":"The molecular machinery of translational control in malaria parasites.","date":"2019","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31531994","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39777415","id":"PMC_39777415","title":"Widespread release of translational repression across Plasmodium's host-to-vector transmission event.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/39777415","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NOT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38352447","id":"PMC_38352447","title":"Global Release of Translational Repression Across Plasmodium's Host-to-Vector Transmission Event.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38352447","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NOT1-G","NOT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5896,"output_tokens":935,"usd":0.015856,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5669,"output_tokens":2038,"usd":0.039648,"stage2_stop_reason":"end_turn"},"total_usd":0.055504,"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\": 2024,\n      \"finding\": \"In P. yoelii female gametocytes, DOZI (DDX6 orthologue) interacts with NOT1-G (PF3D7_1103800 orthologue), and upon fertilization (zygote stage) this interaction is replaced by an interaction between DOZI and the canonical NOT1, providing a mechanistic model for how mRNAs are released from translational repression during the host-to-vector transmission event.\",\n      \"method\": \"TurboID-based proximity proteomics across female gametocyte and zygote stages, cross-validated by ultrastructure expansion microscopy and structured illumination microscopy\",\n      \"journal\": \"bioRxiv : the preprint server for biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — proximity proteomics with microscopy cross-validation in a single lab; preprint, not yet peer-reviewed at time of this entry\",\n      \"pmids\": [\"38352447\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In P. yoelii female gametocytes, DOZI exchanges its interaction from NOT1-G (PF3D7_1103800 orthologue) to the canonical NOT1 in zygotes, as determined by TurboID-based proximity proteomics; this compositional switch in the DOZI/CITH/ALBA complex is consistent with a trigger for the release of mRNAs from translational repression upon fertilization.\",\n      \"method\": \"TurboID-based proximity proteomics (DIA-MS) comparing female gametocytes and zygotes; supported by comparative transcriptomics and proteomics\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity proteomics with quantitative DIA-MS in peer-reviewed publication, single lab but two orthogonal approaches (proximity proteomics + microscopy)\",\n      \"pmids\": [\"39777415\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"NOT1-G (PF3D7_1103800) was identified bioinformatically as a component of the PfCaf1-CCR4-NOT complex in P. falciparum through comparative interactome analysis using human and Plasmodium protein-protein interaction datasets.\",\n      \"method\": \"Bioinformatic/comparative interactome analysis; protein-protein interaction network construction using Cytoscape\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct experimental validation of NOT1-G specifically\",\n      \"pmids\": [\"26525978\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"NOT1-G (PF3D7_1103800) is a subunit of the CAF1/CCR4/NOT complex in Plasmodium that associates with DOZI in female gametocytes to maintain translational repression of specific mRNAs; upon fertilization, DOZI exchanges NOT1-G for the canonical NOT1 in zygotes, providing a mechanistic switch for the global release of translational repression during host-to-vector transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NOT1-G (PF3D7_1103800) is a Plasmodium-specific scaffold subunit associated with the CAF1/CCR4/NOT complex that functions in the stage-specific control of translational repression during malaria parasite transmission [#0, #1]. In P. yoelii female gametocytes, NOT1-G engages the DDX6-family helicase DOZI, and this interaction is a defining feature of the repressed state; upon fertilization, DOZI exchanges NOT1-G for the canonical NOT1 in the zygote, a compositional switch within the DOZI/CITH/ALBA complex that provides a mechanistic trigger for the global release of stored mRNAs from translational repression during the host-to-vector transition [#0, #1]. Its membership in the PfCaf1-CCR4-NOT complex was first predicted bioinformatically in P. falciparum [#2]. Beyond this DOZI-dependent scaffold role in transmission-stage translational control, no direct enzymatic activity, substrate mRNA repertoire, or structural detail for NOT1-G has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Before any functional work, it was unknown whether NOT1-G belonged to the parasite CCR4-NOT machinery at all; comparative interactome analysis placed it within the PfCaf1-CCR4-NOT complex, establishing a candidate role in mRNA regulation.\",\n      \"evidence\": \"Bioinformatic comparative interactome analysis and protein-protein interaction network construction in P. falciparum\",\n      \"pmids\": [\"26525978\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, with no direct experimental validation of NOT1-G specifically\",\n        \"No demonstration of physical interaction or subcellular context\",\n        \"No stage-specific or functional assignment\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown how repressed maternal mRNAs are released from translational silencing at fertilization; proximity proteomics showed DOZI interacts with NOT1-G in female gametocytes and swaps to canonical NOT1 in zygotes, providing a compositional-switch model for derepression during transmission.\",\n      \"evidence\": \"TurboID proximity proteomics across gametocyte and zygote stages, cross-validated by expansion and structured illumination microscopy in P. yoelii (preprint)\",\n      \"pmids\": [\"38352447\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint form at time of entry; proximity proteomics infers association, not direct binding\",\n        \"Does not identify which mRNAs are controlled by the NOT1-G-containing complex\",\n        \"Mechanism driving the NOT1-G-to-NOT1 exchange is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The gametocyte-to-zygote exchange model was extended and quantified, confirming that DOZI shifts from NOT1-G to canonical NOT1 as part of a remodeling of the DOZI/CITH/ALBA complex consistent with a fertilization-triggered release of translational repression.\",\n      \"evidence\": \"TurboID proximity proteomics with quantitative DIA-MS comparing female gametocytes and zygotes, supported by comparative transcriptomics and proteomics in P. yoelii\",\n      \"pmids\": [\"39777415\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study relying on proximity labeling rather than direct structural/biochemical reconstitution\",\n        \"Functional consequence of removing NOT1-G on mRNA derepression not directly tested\",\n        \"Structural basis for DOZI selecting NOT1-G versus NOT1 unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular activity of NOT1-G, its specific mRNA targets, and the structural basis for its stage-specific exchange with canonical NOT1 remain undetermined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined biochemical or scaffolding activity for NOT1-G in isolation\",\n        \"No identified repressed transcript repertoire dependent on NOT1-G\",\n        \"No structural model of the DOZI–NOT1-G interaction or the exchange mechanism\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0006402\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"CAF1/CCR4/NOT (PfCaf1-CCR4-NOT) complex\",\n      \"DOZI/CITH/ALBA translational repression complex\"\n    ],\n    \"partners\": [\n      \"DOZI (DDX6 orthologue)\",\n      \"canonical NOT1\"\n    ],\n    \"other_free_text\": [\n      \"Findings on the DOZI–NOT1-G interaction and its gametocyte-to-zygote exchange derive from P. yoelii; the original complex-membership assignment derives from P. falciparum bioinformatics.\",\n      \"Proposed to act as a stage-specific scaffold whose replacement by canonical NOT1 at fertilization triggers release of maternal mRNAs from translational repression during host-to-vector transmission.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1103800","name":null,"product":"CCR4-NOT transcription complex subunit NOT1-G, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0943100","name":null,"product":"CCR4-NOT transcription complex subunit 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0901400","name":null,"product":"CCR4-NOT transcription complex subunit NOT1-G, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NOT1-G","evaluation":null}