{"gene":"PF3D7_1207600","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2022,"finding":"Knockout of MiaA (PF3D7_1207600), the sole isoprenoid-dependent tRNA prenylation enzyme in the apicoplast, has no effect on blood-stage parasite viability and no effect on apicoplast biogenesis, demonstrating that tRNA prenylation by MiaA cannot explain the apicoplast's reliance on IPP synthesis.","method":"Genetic knockout of MiaA in P. falciparum blood-stage parasites with phenotypic readout of parasite growth and apicoplast biogenesis","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with defined cellular phenotype (apicoplast biogenesis and parasite viability), single lab, single paper","pmids":["35257658"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"MiaA (PF3D7_1207600) acts as a tRNA isopentenyltransferase, using DMAPP to isopentenylate the N6-nitrogen of adenine at base 37 (A37) of a subset of tRNAs that read codons beginning with uridine, generating the i6A37 modification; MiaB acts downstream of MiaA to further methylthiolate this modification.","method":"Inference from bacterial ortholog biochemistry and pathway context described in the context of genetic deletion studies of downstream enzyme MiaB in P. falciparum","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 4 / Weak — enzymatic activity attributed by orthology and pathway annotation, not directly demonstrated in P. falciparum; no direct in vitro assay of MiaA itself reported in these abstracts","pmids":["35164549"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"MiaA (PF3D7_1207600) is annotated as a tRNA dimethylallyltransferase predicted to isopentenylate adenosine at position 37 of specific apicoplast tRNAs using DMAPP, but genetic knockout in P. falciparum blood-stage parasites shows it is dispensable for parasite viability and apicoplast biogenesis, indicating its tRNA prenylation activity is not the mechanism by which IPP supports apicoplast maintenance."},"narrative":{"mechanistic_narrative":"MiaA (PF3D7_1207600) is annotated as the sole isoprenoid-dependent tRNA prenylation enzyme in the P. falciparum apicoplast [PMID:35257658]. Genetic knockout of MiaA in blood-stage parasites has no effect on parasite viability or apicoplast biogenesis, establishing that tRNA prenylation by MiaA cannot account for the apicoplast's dependence on IPP synthesis [PMID:35257658]. Beyond this dispensability phenotype, no direct biochemical characterization of MiaA itself has been established in the available corpus; its assignment as a tRNA isopentenyltransferase that uses DMAPP to generate the i6A37 modification rests on bacterial orthology rather than direct in vitro demonstration [PMID:35164549].","teleology":[{"year":2022,"claim":"The field asked whether the apicoplast's reliance on isoprenoid (IPP) synthesis could be explained by tRNA prenylation; deleting the only enzyme carrying out this reaction tested that hypothesis directly.","evidence":"Genetic knockout of MiaA in P. falciparum blood-stage parasites with readouts of parasite growth and apicoplast biogenesis","pmids":["35257658"],"confidence":"Medium","gaps":["Does not establish MiaA's biochemical activity in P. falciparum","Does not identify which IPP-dependent process explains apicoplast reliance on isoprenoid synthesis","Phenotype assessed only in blood stage; other life-cycle stages not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"To place MiaA in the tRNA modification pathway, its activity was inferred as the upstream isopentenyltransferase generating i6A37, with MiaB acting downstream to methylthiolate the modification.","evidence":"Pathway inference from bacterial ortholog biochemistry, described in the context of genetic deletion studies of the downstream enzyme MiaB in P. falciparum","pmids":["35164549"],"confidence":"Low","gaps":["MiaA enzymatic activity attributed by orthology, not demonstrated in vitro or in P. falciparum","tRNA substrates of MiaA not experimentally defined in P. falciparum","The finding centers on MiaB; MiaA's own role is only inferred as upstream"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what biochemical function MiaA performs directly in P. falciparum and, given its dispensability, what IPP-dependent process it might contribute to, if any.","evidence":"No direct in vitro or in vivo enzymatic assay of MiaA reported in the corpus","pmids":[],"confidence":"Low","gaps":["No direct demonstration of MiaA tRNA isopentenyltransferase activity","No identification of MiaA-modified tRNA substrates in P. falciparum","No structural model or partner interaction data for MiaA"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MIAB (DOWNSTREAM METHYLTHIOLATION ENZYME, PER PATHWAY INFERENCE [#1])"],"other_free_text":["MiaA (PF3D7_1207600) is dispensable for blood-stage parasite viability and apicoplast biogenesis, showing its tRNA prenylation activity does not explain the apicoplast's dependence on IPP synthesis [#0].","MiaA's assignment as a DMAPP-dependent tRNA isopentenyltransferase generating i6A37 is by bacterial orthology, not by direct assay in P. falciparum [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"35257658","id":"PMC_35257658","title":"Critical role for isoprenoids in apicoplast biogenesis by malaria parasites.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35257658","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MiaA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37883328","id":"","title":"The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37883328","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MiaA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35164549","id":"","title":"Roles of Ferredoxin-Dependent Proteins in the Apicoplast of Plasmodium falciparum Parasites.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35164549","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MiaA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24086138","id":"","title":"The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/24086138","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MiaA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6607,"output_tokens":691,"usd":0.015093,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5330,"output_tokens":1575,"usd":0.033013,"stage2_stop_reason":"end_turn"},"total_usd":0.048106,"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\": 2022,\n      \"finding\": \"Knockout of MiaA (PF3D7_1207600), the sole isoprenoid-dependent tRNA prenylation enzyme in the apicoplast, has no effect on blood-stage parasite viability and no effect on apicoplast biogenesis, demonstrating that tRNA prenylation by MiaA cannot explain the apicoplast's reliance on IPP synthesis.\",\n      \"method\": \"Genetic knockout of MiaA in P. falciparum blood-stage parasites with phenotypic readout of parasite growth and apicoplast biogenesis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with defined cellular phenotype (apicoplast biogenesis and parasite viability), single lab, single paper\",\n      \"pmids\": [\"35257658\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MiaA (PF3D7_1207600) acts as a tRNA isopentenyltransferase, using DMAPP to isopentenylate the N6-nitrogen of adenine at base 37 (A37) of a subset of tRNAs that read codons beginning with uridine, generating the i6A37 modification; MiaB acts downstream of MiaA to further methylthiolate this modification.\",\n      \"method\": \"Inference from bacterial ortholog biochemistry and pathway context described in the context of genetic deletion studies of downstream enzyme MiaB in P. falciparum\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — enzymatic activity attributed by orthology and pathway annotation, not directly demonstrated in P. falciparum; no direct in vitro assay of MiaA itself reported in these abstracts\",\n      \"pmids\": [\"35164549\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"MiaA (PF3D7_1207600) is annotated as a tRNA dimethylallyltransferase predicted to isopentenylate adenosine at position 37 of specific apicoplast tRNAs using DMAPP, but genetic knockout in P. falciparum blood-stage parasites shows it is dispensable for parasite viability and apicoplast biogenesis, indicating its tRNA prenylation activity is not the mechanism by which IPP supports apicoplast maintenance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MiaA (PF3D7_1207600) is annotated as the sole isoprenoid-dependent tRNA prenylation enzyme in the P. falciparum apicoplast [#0]. Genetic knockout of MiaA in blood-stage parasites has no effect on parasite viability or apicoplast biogenesis, establishing that tRNA prenylation by MiaA cannot account for the apicoplast's dependence on IPP synthesis [#0]. Beyond this dispensability phenotype, no direct biochemical characterization of MiaA itself has been established in the available corpus; its assignment as a tRNA isopentenyltransferase that uses DMAPP to generate the i6A37 modification rests on bacterial orthology rather than direct in vitro demonstration [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"The field asked whether the apicoplast's reliance on isoprenoid (IPP) synthesis could be explained by tRNA prenylation; deleting the only enzyme carrying out this reaction tested that hypothesis directly.\",\n      \"evidence\": \"Genetic knockout of MiaA in P. falciparum blood-stage parasites with readouts of parasite growth and apicoplast biogenesis\",\n      \"pmids\": [\"35257658\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not establish MiaA's biochemical activity in P. falciparum\",\n        \"Does not identify which IPP-dependent process explains apicoplast reliance on isoprenoid synthesis\",\n        \"Phenotype assessed only in blood stage; other life-cycle stages not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To place MiaA in the tRNA modification pathway, its activity was inferred as the upstream isopentenyltransferase generating i6A37, with MiaB acting downstream to methylthiolate the modification.\",\n      \"evidence\": \"Pathway inference from bacterial ortholog biochemistry, described in the context of genetic deletion studies of the downstream enzyme MiaB in P. falciparum\",\n      \"pmids\": [\"35164549\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"MiaA enzymatic activity attributed by orthology, not demonstrated in vitro or in P. falciparum\",\n        \"tRNA substrates of MiaA not experimentally defined in P. falciparum\",\n        \"The finding centers on MiaB; MiaA's own role is only inferred as upstream\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what biochemical function MiaA performs directly in P. falciparum and, given its dispensability, what IPP-dependent process it might contribute to, if any.\",\n      \"evidence\": \"No direct in vitro or in vivo enzymatic assay of MiaA reported in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct demonstration of MiaA tRNA isopentenyltransferase activity\",\n        \"No identification of MiaA-modified tRNA substrates in P. falciparum\",\n        \"No structural model or partner interaction data for MiaA\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0052381\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009507\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006400\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MiaB (downstream methylthiolation enzyme, per pathway inference [#1])\"],\n    \"other_free_text\": [\n      \"MiaA (PF3D7_1207600) is dispensable for blood-stage parasite viability and apicoplast biogenesis, showing its tRNA prenylation activity does not explain the apicoplast's dependence on IPP synthesis [#0].\",\n      \"MiaA's assignment as a DMAPP-dependent tRNA isopentenyltransferase generating i6A37 is by bacterial orthology, not by direct assay in P. falciparum [#1].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1207600","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0622200, PF3D7_0623200). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1207600","name":null,"product":"tRNA dimethylallyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0606100","name":null,"product":"tRNA dimethylallyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1307500","name":null,"product":"tRNA dimethylallyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MiaA","evaluation":null}