{"gene":"PF3D7_1359400","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2014,"finding":"CELF1 (PF3D7_1359400) demonstrated RNA binding activity in vitro, as measured by UV-crosslinking and electrophoretic mobility shift assays with 12-mer RNA sequences, whereas the paralog CELF2 was RNA-binding negative under the same conditions.","method":"UV-crosslinking assay, electrophoretic mobility shift assay (EMSA)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro RNA-binding assays (UV-crosslinking and EMSA) performed in a single lab with no independent replication","pmids":["25447287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"CELF1 (PF3D7_1359400) localizes to both the nucleus and cytoplasm of asexual intraerythrocytic stage parasites, as demonstrated by GFP-tagged transgenic parasite lines, with individual cells showing either predominantly nuclear or predominantly cytoplasmic distribution, suggesting nucleocytoplasmic shuttling.","method":"GFP-tagged transgenic parasite live-cell imaging and fluorescence microscopy","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment with GFP-tagged transgenic lines in a single lab, no independent replication","pmids":["25447287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"CELF1 (PF3D7_1359400) binds approximately 1376 features from 1040 mRNAs in asexual stage parasites, as identified by RNA immunoprecipitation followed by DNA microarray analysis (ribonomics). A UG-rich sequence motif — similar to the CELF-family binding motif found in introns of other species — was identified among the target mRNAs, suggesting a role in pre-mRNA splicing regulation.","method":"RNA immunoprecipitation (RIP) coupled to DNA microarray (ribonomics); bioinformatic motif analysis","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — RIP-microarray identifies targets with motif analysis in a single lab, no functional validation of splicing role","pmids":["25447287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"CELF1 (PF3D7_1359400) was experimentally captured as an mRNA-binding protein in P. falciparum asexual blood stages using mRNA interactome capture (oligo-dT pulldown followed by mass spectrometry), confirming its interaction with mRNA in vivo.","method":"mRNA interactome capture (oligo-dT pulldown) followed by quantitative mass spectrometry","journal":"Genome biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — experimentally validated mRNA binding in vivo by interactome capture, consistent with independent in vitro evidence from PMID 25447287","pmids":["27381095"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"CELF1 (PF3D7_1359400) was identified as a component of PfDOZI-associated stress granule-like mRNPs in P. falciparum schizonts, co-immunoprecipitating with PfDOZI along with other stress granule markers (eIF4A, eIF4E, PABP1, Alba proteins, ribosomal proteins).","method":"GFP-trap immunoprecipitation of PfDOZI::GFP followed by mass spectrometry","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single Co-IP/MS experiment identifying CELF1 as a PfDOZI-associated protein in schizonts, single lab","pmids":["38702310"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"CELF1 (PF3D7_1359400) co-purified with PF3D7_0823200 (a validated RNA-binding protein) in immunoprecipitation-mass spectrometry experiments from P. falciparum 3D7 asexual stage parasites, indicating membership in a common protein complex. The sucrose-gradient co-segregation (R-DeeP) correlation was low (−0.67), suggesting CELF1 may be a component of multiple distinct complexes.","method":"Immunoprecipitation followed by mass spectrometry (IP-MS); sucrose density gradient ultracentrifugation (R-DeeP)","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment; low co-segregation correlation suggests indirect or complex-dependent association; single lab","pmids":["38355719"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2025,"finding":"CELF1 (PF3D7_1359400) was detected as a stage-dependent proximity interactor of ALBA4 in P. yoelii female gametocytes (but not in zygotes) by TurboID-based proximity proteomics, placing CELF1 within the DOZI/CITH/ALBA translational control complex specifically in female gametocytes.","method":"TurboID-based proximity labeling proteomics (BioID) of DOZI and ALBA4 in gametocytes and zygotes","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — proximity proteomics in a single study; stage-dependent interaction pattern identified but no direct functional validation of CELF1's role","pmids":["39777415"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"CELF1 (PF3D7_1359400) is a bona fide RNA-binding protein in Plasmodium falciparum that shuttles between the nucleus and cytoplasm during asexual blood stages, binds a large repertoire of mRNAs containing a UG-rich intronic motif (consistent with a role in pre-mRNA splicing), and associates with stress granule-like mRNPs containing PfDOZI and other translational regulators in schizonts and with the DOZI/CITH/ALBA4 translational control complex in female gametocytes, suggesting stage-specific roles in post-transcriptional RNA regulation."},"narrative":{"mechanistic_narrative":"CELF1 (PF3D7_1359400) is a bona fide RNA-binding protein of Plasmodium that participates in post-transcriptional RNA regulation across the parasite life cycle [PMID:25447287, PMID:27381095]. In P. falciparum it binds RNA directly in vitro by UV-crosslinking and EMSA — an activity absent from its paralog CELF2 under identical conditions [PMID:25447287] — and is captured on mRNA in vivo by oligo-dT interactome capture [PMID:27381095]. During asexual blood stages it associates with a large mRNA repertoire (~1376 features from ~1040 mRNAs) enriched for a UG-rich motif resembling the intronic CELF-family binding motif of other species, consistent with a role in pre-mRNA splicing regulation [PMID:25447287], and the GFP-tagged protein distributes between the nucleus and cytoplasm in a manner indicative of nucleocytoplasmic shuttling [PMID:25447287]. CELF1 further engages translational-control machinery in a stage-specific fashion: in P. falciparum schizonts it co-immunoprecipitates with PfDOZI-associated stress granule-like mRNPs containing eIF4A, eIF4E, PABP1, Alba and ribosomal proteins [PMID:38702310], and in P. yoelii it is a proximity interactor of ALBA4 within the DOZI/CITH/ALBA translational control complex specifically in female gametocytes but not zygotes [PMID:39777415]. Beyond these binding and association data, the functional consequences of CELF1's RNA binding — including any direct role in splicing or translational repression — have not been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Whether PF3D7_1359400 is a genuine RNA-binding protein was unknown; direct biochemistry established that it binds RNA and distinguished it from its non-binding paralog.","evidence":"UV-crosslinking and EMSA with 12-mer RNAs, comparing CELF1 and CELF2 in P. falciparum","pmids":["25447287"],"confidence":"Medium","gaps":["No independent replication of the in vitro binding assay","Sequence specificity and affinity not quantified","No structural basis for the CELF1 vs CELF2 difference"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"The subcellular compartment in which CELF1 acts was unknown; GFP tagging showed dual nuclear/cytoplasmic distribution, consistent with nucleocytoplasmic shuttling and dual-compartment function.","evidence":"GFP-tagged transgenic P. falciparum live-cell imaging in asexual stages","pmids":["25447287"],"confidence":"Medium","gaps":["Cell-to-cell variability in distribution not mechanistically explained","Shuttling signals or regulatory triggers not identified","Single lab, no independent confirmation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"The RNA targets of CELF1 and its likely regulatory role were undefined; ribonomics identified a large bound mRNA set and a UG-rich intronic-type motif, implicating CELF1 in pre-mRNA splicing regulation.","evidence":"RNA immunoprecipitation coupled to DNA microarray with motif analysis in P. falciparum asexual stages","pmids":["25447287"],"confidence":"Medium","gaps":["No functional validation of a splicing role","Direct vs indirect binding to targets not distinguished","Motif not experimentally confirmed as the binding determinant"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Whether CELF1 binds mRNA inside living parasites (not only in vitro) was unresolved; interactome capture confirmed in vivo mRNA association.","evidence":"Oligo-dT mRNA interactome capture with quantitative mass spectrometry in P. falciparum blood stages","pmids":["27381095"],"confidence":"Medium","gaps":["Does not identify which mRNAs are bound in vivo","No link between capture and a specific regulatory outcome"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Whether CELF1 participates in higher-order mRNP assemblies was unknown; Co-IP placed it within PfDOZI-associated stress granule-like mRNPs in schizonts alongside translational regulators.","evidence":"GFP-trap immunoprecipitation of PfDOZI::GFP followed by mass spectrometry in P. falciparum schizonts","pmids":["38702310"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation","Direct vs RNA-bridged association not resolved","CELF1's specific function within the granule not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Whether CELF1 belongs to a defined protein complex was addressed by IP-MS and gradient co-segregation, indicating co-purification with an RNA-binding protein but likely membership in multiple distinct complexes.","evidence":"IP-MS and sucrose-gradient R-DeeP with PF3D7_0823200 in P. falciparum 3D7 asexual stages","pmids":["38355719"],"confidence":"Low","gaps":["Low co-segregation correlation (−0.67) suggests indirect or complex-dependent association not independently confirmed","Single Co-IP experiment","Composition of the distinct complexes not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2025,"claim":"Whether CELF1 engages translational-control machinery in transmission stages was unknown; proximity proteomics placed it in the DOZI/CITH/ALBA complex specifically in female gametocytes.","evidence":"TurboID proximity labeling of DOZI and ALBA4 in P. yoelii female gametocytes versus zygotes","pmids":["39777415"],"confidence":"Medium","gaps":["Stage-dependent interaction not functionally validated","Shown in P. yoelii; not confirmed for P. falciparum gametocytes","Proximity does not establish direct binding"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"The direct functional consequence of CELF1 RNA binding — whether it regulates pre-mRNA splicing, mRNA stability, or translational repression — remains undetermined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function or genetic knockout phenotype reported","No demonstrated effect on splicing of target transcripts","Direct RNA targets in vivo not mapped at nucleotide resolution"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfDOZI-associated stress granule-like mRNP (schizonts) [#4]","DOZI/CITH/ALBA translational control complex (female gametocytes, P. yoelii) [#6]","Complex co-purifying with PF3D7_0823200 (asexual stages) [#5]"],"partners":["PFDOZI [#4]","EIF4A [#4]","EIF4E [#4]","PABP1 [#4]","ALBA PROTEINS [#4]","ALBA4 [#6]","PF3D7_0823200 [#5]"],"other_free_text":["Binds ~1376 features from ~1040 asexual-stage mRNAs enriched for a UG-rich CELF-family-type motif [#2]","RNA-binding activity contrasts with the non-binding paralog CELF2 [#0]","Low sucrose-gradient co-segregation (R-DeeP −0.67) indicates possible membership in multiple distinct complexes [#5]","ALBA4 proximity association is stage-restricted: present in female gametocytes but not zygotes (P. yoelii) [#6]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25447287","id":"PMC_25447287","title":"Molecular characterization of Plasmodium falciparum Bruno/CELF RNA binding proteins.","date":"2014","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/25447287","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfCELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42218151","id":"","title":"Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42218151","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38355719","id":"","title":"Proteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38355719","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39777415","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"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":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36331983","id":"","title":"Transcriptomic complexity of the human malaria parasite Plasmodium falciparum revealed by long-read sequencing.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36331983","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38702310","id":"","title":"The DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38702310","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34673764","id":"","title":"The Plasmodium NOT1-G paralogue is an essential regulator of sexual stage maturation and parasite transmission.","date":"2021","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/34673764","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26525978","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29985403","id":"","title":"Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29985403","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27381095","id":"","title":"The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum.","date":"2016","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/27381095","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26415947","id":"","title":"The PfAlba1 RNA-binding protein is an important regulator of translational timing in Plasmodium falciparum blood stages.","date":"2015","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/26415947","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CELF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15208,"output_tokens":1992,"usd":0.037752,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7176,"output_tokens":3462,"usd":0.061215,"stage2_stop_reason":"end_turn"},"total_usd":0.098967,"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\": 2014,\n      \"finding\": \"CELF1 (PF3D7_1359400) demonstrated RNA binding activity in vitro, as measured by UV-crosslinking and electrophoretic mobility shift assays with 12-mer RNA sequences, whereas the paralog CELF2 was RNA-binding negative under the same conditions.\",\n      \"method\": \"UV-crosslinking assay, electrophoretic mobility shift assay (EMSA)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro RNA-binding assays (UV-crosslinking and EMSA) performed in a single lab with no independent replication\",\n      \"pmids\": [\"25447287\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CELF1 (PF3D7_1359400) localizes to both the nucleus and cytoplasm of asexual intraerythrocytic stage parasites, as demonstrated by GFP-tagged transgenic parasite lines, with individual cells showing either predominantly nuclear or predominantly cytoplasmic distribution, suggesting nucleocytoplasmic shuttling.\",\n      \"method\": \"GFP-tagged transgenic parasite live-cell imaging and fluorescence microscopy\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment with GFP-tagged transgenic lines in a single lab, no independent replication\",\n      \"pmids\": [\"25447287\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CELF1 (PF3D7_1359400) binds approximately 1376 features from 1040 mRNAs in asexual stage parasites, as identified by RNA immunoprecipitation followed by DNA microarray analysis (ribonomics). A UG-rich sequence motif — similar to the CELF-family binding motif found in introns of other species — was identified among the target mRNAs, suggesting a role in pre-mRNA splicing regulation.\",\n      \"method\": \"RNA immunoprecipitation (RIP) coupled to DNA microarray (ribonomics); bioinformatic motif analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — RIP-microarray identifies targets with motif analysis in a single lab, no functional validation of splicing role\",\n      \"pmids\": [\"25447287\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CELF1 (PF3D7_1359400) was experimentally captured as an mRNA-binding protein in P. falciparum asexual blood stages using mRNA interactome capture (oligo-dT pulldown followed by mass spectrometry), confirming its interaction with mRNA in vivo.\",\n      \"method\": \"mRNA interactome capture (oligo-dT pulldown) followed by quantitative mass spectrometry\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — experimentally validated mRNA binding in vivo by interactome capture, consistent with independent in vitro evidence from PMID 25447287\",\n      \"pmids\": [\"27381095\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CELF1 (PF3D7_1359400) was identified as a component of PfDOZI-associated stress granule-like mRNPs in P. falciparum schizonts, co-immunoprecipitating with PfDOZI along with other stress granule markers (eIF4A, eIF4E, PABP1, Alba proteins, ribosomal proteins).\",\n      \"method\": \"GFP-trap immunoprecipitation of PfDOZI::GFP followed by mass spectrometry\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single Co-IP/MS experiment identifying CELF1 as a PfDOZI-associated protein in schizonts, single lab\",\n      \"pmids\": [\"38702310\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CELF1 (PF3D7_1359400) co-purified with PF3D7_0823200 (a validated RNA-binding protein) in immunoprecipitation-mass spectrometry experiments from P. falciparum 3D7 asexual stage parasites, indicating membership in a common protein complex. The sucrose-gradient co-segregation (R-DeeP) correlation was low (−0.67), suggesting CELF1 may be a component of multiple distinct complexes.\",\n      \"method\": \"Immunoprecipitation followed by mass spectrometry (IP-MS); sucrose density gradient ultracentrifugation (R-DeeP)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment; low co-segregation correlation suggests indirect or complex-dependent association; single lab\",\n      \"pmids\": [\"38355719\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CELF1 (PF3D7_1359400) was detected as a stage-dependent proximity interactor of ALBA4 in P. yoelii female gametocytes (but not in zygotes) by TurboID-based proximity proteomics, placing CELF1 within the DOZI/CITH/ALBA translational control complex specifically in female gametocytes.\",\n      \"method\": \"TurboID-based proximity labeling proteomics (BioID) of DOZI and ALBA4 in gametocytes and zygotes\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — proximity proteomics in a single study; stage-dependent interaction pattern identified but no direct functional validation of CELF1's role\",\n      \"pmids\": [\"39777415\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CELF1 (PF3D7_1359400) is a bona fide RNA-binding protein in Plasmodium falciparum that shuttles between the nucleus and cytoplasm during asexual blood stages, binds a large repertoire of mRNAs containing a UG-rich intronic motif (consistent with a role in pre-mRNA splicing), and associates with stress granule-like mRNPs containing PfDOZI and other translational regulators in schizonts and with the DOZI/CITH/ALBA4 translational control complex in female gametocytes, suggesting stage-specific roles in post-transcriptional RNA regulation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CELF1 (PF3D7_1359400) is a bona fide RNA-binding protein of Plasmodium that participates in post-transcriptional RNA regulation across the parasite life cycle [#0, #3]. In P. falciparum it binds RNA directly in vitro by UV-crosslinking and EMSA — an activity absent from its paralog CELF2 under identical conditions [#0] — and is captured on mRNA in vivo by oligo-dT interactome capture [#3]. During asexual blood stages it associates with a large mRNA repertoire (~1376 features from ~1040 mRNAs) enriched for a UG-rich motif resembling the intronic CELF-family binding motif of other species, consistent with a role in pre-mRNA splicing regulation [#2], and the GFP-tagged protein distributes between the nucleus and cytoplasm in a manner indicative of nucleocytoplasmic shuttling [#1]. CELF1 further engages translational-control machinery in a stage-specific fashion: in P. falciparum schizonts it co-immunoprecipitates with PfDOZI-associated stress granule-like mRNPs containing eIF4A, eIF4E, PABP1, Alba and ribosomal proteins [#4], and in P. yoelii it is a proximity interactor of ALBA4 within the DOZI/CITH/ALBA translational control complex specifically in female gametocytes but not zygotes [#6]. Beyond these binding and association data, the functional consequences of CELF1's RNA binding — including any direct role in splicing or translational repression — have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether PF3D7_1359400 is a genuine RNA-binding protein was unknown; direct biochemistry established that it binds RNA and distinguished it from its non-binding paralog.\",\n      \"evidence\": \"UV-crosslinking and EMSA with 12-mer RNAs, comparing CELF1 and CELF2 in P. falciparum\",\n      \"pmids\": [\"25447287\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No independent replication of the in vitro binding assay\", \"Sequence specificity and affinity not quantified\", \"No structural basis for the CELF1 vs CELF2 difference\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The subcellular compartment in which CELF1 acts was unknown; GFP tagging showed dual nuclear/cytoplasmic distribution, consistent with nucleocytoplasmic shuttling and dual-compartment function.\",\n      \"evidence\": \"GFP-tagged transgenic P. falciparum live-cell imaging in asexual stages\",\n      \"pmids\": [\"25447287\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Cell-to-cell variability in distribution not mechanistically explained\", \"Shuttling signals or regulatory triggers not identified\", \"Single lab, no independent confirmation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The RNA targets of CELF1 and its likely regulatory role were undefined; ribonomics identified a large bound mRNA set and a UG-rich intronic-type motif, implicating CELF1 in pre-mRNA splicing regulation.\",\n      \"evidence\": \"RNA immunoprecipitation coupled to DNA microarray with motif analysis in P. falciparum asexual stages\",\n      \"pmids\": [\"25447287\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No functional validation of a splicing role\", \"Direct vs indirect binding to targets not distinguished\", \"Motif not experimentally confirmed as the binding determinant\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether CELF1 binds mRNA inside living parasites (not only in vitro) was unresolved; interactome capture confirmed in vivo mRNA association.\",\n      \"evidence\": \"Oligo-dT mRNA interactome capture with quantitative mass spectrometry in P. falciparum blood stages\",\n      \"pmids\": [\"27381095\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Does not identify which mRNAs are bound in vivo\", \"No link between capture and a specific regulatory outcome\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether CELF1 participates in higher-order mRNP assemblies was unknown; Co-IP placed it within PfDOZI-associated stress granule-like mRNPs in schizonts alongside translational regulators.\",\n      \"evidence\": \"GFP-trap immunoprecipitation of PfDOZI::GFP followed by mass spectrometry in P. falciparum schizonts\",\n      \"pmids\": [\"38702310\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation\", \"Direct vs RNA-bridged association not resolved\", \"CELF1's specific function within the granule not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether CELF1 belongs to a defined protein complex was addressed by IP-MS and gradient co-segregation, indicating co-purification with an RNA-binding protein but likely membership in multiple distinct complexes.\",\n      \"evidence\": \"IP-MS and sucrose-gradient R-DeeP with PF3D7_0823200 in P. falciparum 3D7 asexual stages\",\n      \"pmids\": [\"38355719\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Low co-segregation correlation (\\u22120.67) suggests indirect or complex-dependent association not independently confirmed\", \"Single Co-IP experiment\", \"Composition of the distinct complexes not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether CELF1 engages translational-control machinery in transmission stages was unknown; proximity proteomics placed it in the DOZI/CITH/ALBA complex specifically in female gametocytes.\",\n      \"evidence\": \"TurboID proximity labeling of DOZI and ALBA4 in P. yoelii female gametocytes versus zygotes\",\n      \"pmids\": [\"39777415\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Stage-dependent interaction not functionally validated\", \"Shown in P. yoelii; not confirmed for P. falciparum gametocytes\", \"Proximity does not establish direct binding\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct functional consequence of CELF1 RNA binding — whether it regulates pre-mRNA splicing, mRNA stability, or translational repression — remains undetermined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No loss-of-function or genetic knockout phenotype reported\", \"No demonstrated effect on splicing of target transcripts\", \"Direct RNA targets in vivo not mapped at nucleotide resolution\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0003729\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0010494\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0008380\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0006417\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"complexes\": [\n      \"PfDOZI-associated stress granule-like mRNP (schizonts) [#4]\",\n      \"DOZI/CITH/ALBA translational control complex (female gametocytes, P. yoelii) [#6]\",\n      \"Complex co-purifying with PF3D7_0823200 (asexual stages) [#5]\"\n    ],\n    \"partners\": [\n      \"PfDOZI [#4]\",\n      \"eIF4A [#4]\",\n      \"eIF4E [#4]\",\n      \"PABP1 [#4]\",\n      \"Alba proteins [#4]\",\n      \"ALBA4 [#6]\",\n      \"PF3D7_0823200 [#5]\"\n    ],\n    \"other_free_text\": [\n      \"Binds ~1376 features from ~1040 asexual-stage mRNAs enriched for a UG-rich CELF-family-type motif [#2]\",\n      \"RNA-binding activity contrasts with the non-binding paralog CELF2 [#0]\",\n      \"Low sucrose-gradient co-segregation (R-DeeP \\u22120.67) indicates possible membership in multiple distinct complexes [#5]\",\n      \"ALBA4 proximity association is stage-restricted: present in female gametocytes but not zygotes (P. yoelii) [#6]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1359400","name":null,"product":"CUGBP Elav-like family member 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1135700","name":null,"product":"CUGBP Elav-like family member 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1111900","name":null,"product":"CUGBP Elav-like family member 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CELF1","evaluation":null}