{"gene":"PF3D7_0923900","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2018,"finding":"The P. yoelii ortholog of PABP2 (PyPABP2) binds specifically and strongly to poly(A) RNA sequences, as demonstrated by multiple independent binding assays. By indirect immunofluorescence assay, PyPABP2 is localized to the nucleus during blood stages, consistent with a nuclear PABP function, in contrast to the cytosolic PyPABP1.","method":"Multiple independent poly(A)-binding assays (in vitro); indirect immunofluorescence assay (IFA) for subcellular localization","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (binding assay and IFA) in a single study establishing poly(A) binding specificity and nuclear localization","pmids":["29359180"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2021,"finding":"In P. falciparum blood stages, PABP2 (PF3D7_0923900) preferentially binds non-methylated poly(A) RNA: it was significantly enriched in pulldowns using a non-methylated RNA oligonucleotide (GGACA repeat) but not in pulldowns using the m6A-methylated version (GGm6ACA repeat), indicating that PABP2 binding is inhibited by m6A modification at adenosines.","method":"Quantitative TMT proteomics following RNA oligonucleotide pulldown comparing methylated vs. non-methylated RNA baits","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative proteomics pulldown with direct comparison of methylated vs. non-methylated baits in a single rigorous study; single lab","pmids":["33906926"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"In P. falciparum, PABP2 was identified as a component of stress granule-like mRNPs formed in nutritionally stressed schizonts, associating with PfDOZI, CITH, and PAIP1 (PABP-interacting protein 1). PABP2 was notably absent from gametocyte germ cell granule-like mRNPs, which instead contained the cytosolic PABP1, indicating stage-specific incorporation of PABP2 into distinct mRNP complexes.","method":"Co-immunoprecipitation/proximity proteomics (PfDOZI interactome) by quantitative mass spectrometry across life stages","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (interactome MS), no reciprocal validation or functional follow-up specific to PABP2","pmids":["38702310"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"In P. yoelii, PABP2 (nuclear PABP) is a stage-independent proximal interactor of ALBA4 in both female gametocytes and zygotes, as revealed by TurboID-based proximity proteomics. PABP2 also appears as a proximal interactor of ALBA4 specifically in zygotes (at the 3' end of mRNAs), indicating its participation in the DOZI/CITH/ALBA regulatory complex across the host-to-vector transmission event.","method":"TurboID-based proximity proteomics (DIA-MS) of ALBA4 and DOZI baits in female gametocytes and zygotes","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proximity labeling approach, single lab; PABP2 is identified as a proximal partner but no functional follow-up specific to PABP2 was performed","pmids":["39777415"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"PABP2 (PF3D7_0923900) is a nuclear-localized poly(A)-binding protein in Plasmodium that binds specifically to non-methylated poly(A) RNA sequences, is excluded from m6A-methylated RNA complexes, associates with the DOZI/CITH/ALBA translational regulatory complex (including ALBA4) in both gametocytes and zygotes, and is recruited into stress granule-like mRNPs in schizonts alongside PfDOZI, CITH, and PAIP1."},"narrative":{"mechanistic_narrative":"PABP2 (PF3D7_0923900) is a nuclear poly(A)-binding protein of Plasmodium that recognizes poly(A) RNA and participates in post-transcriptional mRNP regulation [PMID:29359180, PMID:33906926]. In the P. yoelii ortholog, PABP2 binds poly(A) RNA specifically and strongly and localizes to the nucleus during blood stages, distinguishing it from the cytosolic PABP1 [PMID:29359180]. In P. falciparum, its poly(A) recognition is sensitive to RNA modification: PABP2 is enriched on non-methylated poly(A) RNA but excluded from m6A-methylated RNA, indicating that adenosine m6A methylation inhibits its binding [PMID:33906926]. PABP2 is incorporated into translationally repressive mRNP complexes in a stage-specific manner: in nutritionally stressed P. falciparum schizonts it associates with PfDOZI, CITH, and PAIP1 in stress granule-like mRNPs (while the germ cell granules of gametocytes instead contain PABP1) [PMID:38702310], and in P. yoelii it is a proximal interactor of ALBA4 within the DOZI/CITH/ALBA regulatory complex across female gametocytes and zygotes [PMID:39777415]. Beyond these binding, localization, and complex-membership observations, no dedicated functional or loss-of-function characterization of PABP2 itself has been reported in the available corpus.","teleology":[{"year":2018,"claim":"Establishing that this poly(A)-binding protein is a nuclear, poly(A)-specific factor distinct from the cytosolic PABP1 defined its basic biochemical identity and subcellular compartment.","evidence":"Multiple in vitro poly(A)-binding assays and indirect immunofluorescence in P. yoelii blood stages","pmids":["29359180"],"confidence":"Medium","gaps":["Binding shown for the P. yoelii ortholog; not directly demonstrated for P. falciparum PF3D7_0923900 in this study","No structural basis for poly(A) recognition determined","No functional consequence of nuclear localization established"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2021,"claim":"Showing that PABP2 binding is blocked by m6A methylation linked its RNA recognition to the RNA epitranscriptome, implying it reads a specific chemical state of poly(A) sequences.","evidence":"Quantitative TMT proteomics of methylated vs. non-methylated RNA oligonucleotide pulldowns in P. falciparum blood stages","pmids":["33906926"],"confidence":"Medium","gaps":["Whether m6A exclusion alters mRNA fate or translation regulation was not tested for PABP2","Single-lab, single-method observation without reciprocal in vivo validation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Identifying PABP2 in stress-induced schizont mRNPs with PfDOZI, CITH, and PAIP1 placed it in translational-repression granules and revealed stage-specific use of PABP2 versus cytosolic PABP1.","evidence":"PfDOZI interactome by quantitative mass spectrometry across life stages in P. falciparum","pmids":["38702310"],"confidence":"Low","gaps":["Single interactome MS approach without reciprocal Co-IP or functional follow-up specific to PABP2","Direct versus indirect association within the mRNP unresolved","Role of PABP2 in granule assembly or mRNA fate not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Detecting PABP2 as a proximal ALBA4 interactor in gametocytes and zygotes extended its mRNP association into the DOZI/CITH/ALBA regulatory complex spanning the transmission event.","evidence":"TurboID-based proximity proteomics (DIA-MS) of ALBA4 and DOZI baits in P. yoelii female gametocytes and zygotes","pmids":["39777415"],"confidence":"Low","gaps":["Proximity labeling identifies neighbors, not direct binding; no reciprocal validation for PABP2","No functional or loss-of-function study of PABP2 in this complex","Contribution of PABP2 to translational repression during transmission unknown"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"The direct molecular function of PABP2 within its mRNP complexes and the phenotypic consequence of its loss remain undetermined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout or knockdown of PABP2 reported","Whether PABP2 actively represses translation or merely marks poly(A) tails is untested","Mechanism connecting nuclear localization to cytoplasmic/granule mRNP roles unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["DOZI/CITH/ALBA translational regulatory complex","Stress granule-like mRNP (with PfDOZI, CITH, PAIP1)"],"partners":["PFDOZI","CITH","PAIP1","ALBA4"],"other_free_text":["Binding to poly(A) RNA is inhibited by m6A methylation of adenosine (P. falciparum) [#1]","Nuclear PABP distinct from cytosolic PABP1; PABP2 is stage-specifically incorporated into mRNPs whereas PABP1 populates gametocyte germ cell granules [#0, #2]","Evidence for the DOZI/CITH/ALBA association derives from proximity/interactome proteomics without PABP2-specific functional follow-up [#2, #3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29359180","id":"PMC_29359180","title":"Nuclear, Cytosolic, and Surface-Localized Poly(A)-Binding Proteins of Plasmodium yoelii.","date":"2018","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/29359180","citation_count":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PyPABP2"],"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":["PABP2"],"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":["PABP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37322481","id":"","title":"Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites.","date":"2023","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/37322481","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PABP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33906926","id":"","title":"Functional Characterization of the m6A-Dependent Translational Modulator PfYTH.2 in the Human Malaria Parasite.","date":"2021","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/33906926","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PABP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8809,"output_tokens":1331,"usd":0.023196,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6162,"output_tokens":2506,"usd":0.04673,"stage2_stop_reason":"end_turn"},"total_usd":0.069926,"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\": 2018,\n      \"finding\": \"The P. yoelii ortholog of PABP2 (PyPABP2) binds specifically and strongly to poly(A) RNA sequences, as demonstrated by multiple independent binding assays. By indirect immunofluorescence assay, PyPABP2 is localized to the nucleus during blood stages, consistent with a nuclear PABP function, in contrast to the cytosolic PyPABP1.\",\n      \"method\": \"Multiple independent poly(A)-binding assays (in vitro); indirect immunofluorescence assay (IFA) for subcellular localization\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (binding assay and IFA) in a single study establishing poly(A) binding specificity and nuclear localization\",\n      \"pmids\": [\"29359180\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In P. falciparum blood stages, PABP2 (PF3D7_0923900) preferentially binds non-methylated poly(A) RNA: it was significantly enriched in pulldowns using a non-methylated RNA oligonucleotide (GGACA repeat) but not in pulldowns using the m6A-methylated version (GGm6ACA repeat), indicating that PABP2 binding is inhibited by m6A modification at adenosines.\",\n      \"method\": \"Quantitative TMT proteomics following RNA oligonucleotide pulldown comparing methylated vs. non-methylated RNA baits\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative proteomics pulldown with direct comparison of methylated vs. non-methylated baits in a single rigorous study; single lab\",\n      \"pmids\": [\"33906926\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In P. falciparum, PABP2 was identified as a component of stress granule-like mRNPs formed in nutritionally stressed schizonts, associating with PfDOZI, CITH, and PAIP1 (PABP-interacting protein 1). PABP2 was notably absent from gametocyte germ cell granule-like mRNPs, which instead contained the cytosolic PABP1, indicating stage-specific incorporation of PABP2 into distinct mRNP complexes.\",\n      \"method\": \"Co-immunoprecipitation/proximity proteomics (PfDOZI interactome) by quantitative mass spectrometry across life stages\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (interactome MS), no reciprocal validation or functional follow-up specific to PABP2\",\n      \"pmids\": [\"38702310\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In P. yoelii, PABP2 (nuclear PABP) is a stage-independent proximal interactor of ALBA4 in both female gametocytes and zygotes, as revealed by TurboID-based proximity proteomics. PABP2 also appears as a proximal interactor of ALBA4 specifically in zygotes (at the 3' end of mRNAs), indicating its participation in the DOZI/CITH/ALBA regulatory complex across the host-to-vector transmission event.\",\n      \"method\": \"TurboID-based proximity proteomics (DIA-MS) of ALBA4 and DOZI baits in female gametocytes and zygotes\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proximity labeling approach, single lab; PABP2 is identified as a proximal partner but no functional follow-up specific to PABP2 was performed\",\n      \"pmids\": [\"39777415\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PABP2 (PF3D7_0923900) is a nuclear-localized poly(A)-binding protein in Plasmodium that binds specifically to non-methylated poly(A) RNA sequences, is excluded from m6A-methylated RNA complexes, associates with the DOZI/CITH/ALBA translational regulatory complex (including ALBA4) in both gametocytes and zygotes, and is recruited into stress granule-like mRNPs in schizonts alongside PfDOZI, CITH, and PAIP1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PABP2 (PF3D7_0923900) is a nuclear poly(A)-binding protein of Plasmodium that recognizes poly(A) RNA and participates in post-transcriptional mRNP regulation [#0, #1]. In the P. yoelii ortholog, PABP2 binds poly(A) RNA specifically and strongly and localizes to the nucleus during blood stages, distinguishing it from the cytosolic PABP1 [#0]. In P. falciparum, its poly(A) recognition is sensitive to RNA modification: PABP2 is enriched on non-methylated poly(A) RNA but excluded from m6A-methylated RNA, indicating that adenosine m6A methylation inhibits its binding [#1]. PABP2 is incorporated into translationally repressive mRNP complexes in a stage-specific manner: in nutritionally stressed P. falciparum schizonts it associates with PfDOZI, CITH, and PAIP1 in stress granule-like mRNPs (while the germ cell granules of gametocytes instead contain PABP1) [#2], and in P. yoelii it is a proximal interactor of ALBA4 within the DOZI/CITH/ALBA regulatory complex across female gametocytes and zygotes [#3]. Beyond these binding, localization, and complex-membership observations, no dedicated functional or loss-of-function characterization of PABP2 itself has been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing that this poly(A)-binding protein is a nuclear, poly(A)-specific factor distinct from the cytosolic PABP1 defined its basic biochemical identity and subcellular compartment.\",\n      \"evidence\": \"Multiple in vitro poly(A)-binding assays and indirect immunofluorescence in P. yoelii blood stages\",\n      \"pmids\": [\"29359180\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding shown for the P. yoelii ortholog; not directly demonstrated for P. falciparum PF3D7_0923900 in this study\",\n        \"No structural basis for poly(A) recognition determined\",\n        \"No functional consequence of nuclear localization established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showing that PABP2 binding is blocked by m6A methylation linked its RNA recognition to the RNA epitranscriptome, implying it reads a specific chemical state of poly(A) sequences.\",\n      \"evidence\": \"Quantitative TMT proteomics of methylated vs. non-methylated RNA oligonucleotide pulldowns in P. falciparum blood stages\",\n      \"pmids\": [\"33906926\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether m6A exclusion alters mRNA fate or translation regulation was not tested for PABP2\",\n        \"Single-lab, single-method observation without reciprocal in vivo validation\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying PABP2 in stress-induced schizont mRNPs with PfDOZI, CITH, and PAIP1 placed it in translational-repression granules and revealed stage-specific use of PABP2 versus cytosolic PABP1.\",\n      \"evidence\": \"PfDOZI interactome by quantitative mass spectrometry across life stages in P. falciparum\",\n      \"pmids\": [\"38702310\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single interactome MS approach without reciprocal Co-IP or functional follow-up specific to PABP2\",\n        \"Direct versus indirect association within the mRNP unresolved\",\n        \"Role of PABP2 in granule assembly or mRNA fate not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Detecting PABP2 as a proximal ALBA4 interactor in gametocytes and zygotes extended its mRNP association into the DOZI/CITH/ALBA regulatory complex spanning the transmission event.\",\n      \"evidence\": \"TurboID-based proximity proteomics (DIA-MS) of ALBA4 and DOZI baits in P. yoelii female gametocytes and zygotes\",\n      \"pmids\": [\"39777415\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Proximity labeling identifies neighbors, not direct binding; no reciprocal validation for PABP2\",\n        \"No functional or loss-of-function study of PABP2 in this complex\",\n        \"Contribution of PABP2 to translational repression during transmission unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of PABP2 within its mRNP complexes and the phenotypic consequence of its loss remain undetermined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout or knockdown of PABP2 reported\",\n        \"Whether PABP2 actively represses translation or merely marks poly(A) tails is untested\",\n        \"Mechanism connecting nuclear localization to cytoplasmic/granule mRNP roles unresolved\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008143\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0003729\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0036464\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0006417\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\n      \"DOZI/CITH/ALBA translational regulatory complex\",\n      \"Stress granule-like mRNP (with PfDOZI, CITH, PAIP1)\"\n    ],\n    \"partners\": [\n      \"PfDOZI\",\n      \"CITH\",\n      \"PAIP1\",\n      \"ALBA4\"\n    ],\n    \"other_free_text\": [\n      \"Binding to poly(A) RNA is inhibited by m6A methylation of adenosine (P. falciparum) [#1]\",\n      \"Nuclear PABP distinct from cytosolic PABP1; PABP2 is stage-specifically incorporated into mRNPs whereas PABP1 populates gametocyte germ cell granules [#0, #2]\",\n      \"Evidence for the DOZI/CITH/ALBA association derives from proximity/interactome proteomics without PABP2-specific functional follow-up [#2, #3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0923900","name":null,"product":"polyadenylate-binding protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0824800","name":null,"product":"polyadenylate-binding protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0721900","name":null,"product":"polyadenylate-binding protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PABP2","evaluation":null}