{"gene":"YAE1","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2015,"finding":"Yae1 and Lto1 form a complex that functions as a target-specific adaptor recruiting apo-Rli1 to the generic CIA (cytosolic Fe-S protein assembly) machinery for iron-sulfur cluster insertion. Lto1 uses its conserved C-terminal tryptophan to bind the CIA targeting complex, deca-GX3 motifs in both Yae1 and Lto1 mediate their complex formation, and Yae1 directly recruits Rli1. Human YAE1D1 can replace yeast Yae1, demonstrating evolutionary conservation.","method":"Systematic protein interaction approaches (Co-IP/pulldown), yeast depletion/complementation experiments, domain mutagenesis (C-terminal tryptophan, deca-GX3 motifs), Fe-S cluster maturation assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (protein interaction screens, mutagenesis of specific motifs, functional Fe-S maturation assays, cross-species complementation) in a single rigorous study","pmids":["26182403"],"is_preprint":false},{"year":2013,"finding":"Yae1 bridges the interaction between Lto1 (YNL260c/ORAOV1) and Rli1/ABCE1, forming a trimeric complex. Loss of Lto1 (and by extension this complex) leads to defective 60S ribosomal subunit maturation and abrogated translation initiation. The complex is required for maintaining Rli1/ABCE1 [4Fe-4S] cluster integrity under aerobic conditions. Interactions were demonstrated both in vivo and in vitro.","method":"Yeast conditional mutants, ribosome maturation assays (sucrose gradient fractionation), in vivo and in vitro protein interaction assays (Co-IP, pulldown), genetic complementation with human ORAOV1","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal in vivo and in vitro interaction assays, functional ribosome biogenesis readouts, cross-species complementation, single lab but multiple orthogonal methods","pmids":["23318452"],"is_preprint":false},{"year":2025,"finding":"The LTO1/YAE1 complex regulates nonsense-mediated RNA decay (NMD) and MHC-I antigen presentation in tumor cells. Deficiency of LTO1, YAE1, or their downstream target ABCE1 impairs NMD, causing overexpression of MHC-I regulators NLRC5, IRF1, and NF-κB, resulting in enhanced T cell activation and tumor cell killing. The complex acts upstream of ABCE1 in the NMD pathway.","method":"CRISPR/Cas9 knockouts, overexpression, mutational analysis, fluorescent NMD reporter assays, FACS, RT-qPCR, mRNA decay assays, polysome profiling, TCR-T cell/tumor coculture killing assays, mouse tumor model","journal":"Journal for immunotherapy of cancer","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (CRISPR KO, reporter assays, polysome profiling, in vivo mouse model) in a single study establishing pathway placement upstream of ABCE1/NMD","pmids":["40987494"],"is_preprint":false},{"year":2026,"finding":"In fission yeast Schizosaccharomyces pombe, Tpt1 contains a C-terminal domain (aa 238-365) homologous to budding yeast iron-sulfur cluster assembly factor Yae1. Both the RNA 2'-phosphotransferase catalytic domain and the C-terminal Yae1 domain of SpTpt1 are essential for S. pombe growth, though they need not be covalently linked within the same polypeptide. This identifies the Yae1 domain as a functionally essential, separable module.","method":"Domain deletion/mutational analysis, genetic complementation (split-domain rescue), S. pombe growth assays, sequence homology analysis","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic complementation and mutagenesis in a single study establishing essential nature of the Yae1 domain in fission yeast, but single lab and limited to this organism context","pmids":["41339091"],"is_preprint":false},{"year":2016,"finding":"Yeast strains lacking YAE1 are hypersensitive to the antifungal compound vulpinic acid, and vulpinic acid treatment significantly lowers YAE1 expression; cell cycle arrest in S and G2/M phases is observed under these conditions.","method":"Haploinsufficiency and homozygous-profiling chemical-genetic assays, flow cytometry cell cycle analysis, relative gene expression measurement","journal":"Journal of applied microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — chemogenomic sensitivity screen with single-method validation; establishes genetic requirement for YAE1 under vulpinic acid stress but provides no direct mechanistic insight into YAE1 function","pmids":["27660105"],"is_preprint":false}],"current_model":"YAE1 (human YAE1D1) forms a conserved adaptor complex with LTO1/ORAOV1 that recruits apo-ABCE1/Rli1 to the CIA machinery for iron-sulfur cluster insertion via a chain of binding events (LTO1 C-terminal tryptophan contacts the CIA targeting complex, deca-GX3 motifs mediate Yae1-Lto1 heterodimerization, and Yae1 directly recruits ABCE1); this complex is required for 60S ribosome biogenesis, translation initiation, and—by enabling ABCE1 function—also suppresses nonsense-mediated mRNA decay and thereby dampens MHC-I antigen presentation in tumor cells."},"narrative":{"mechanistic_narrative":"YAE1 (human YAE1D1) is a target-specific adaptor that delivers apo-ABCE1/Rli1 to the cytosolic iron-sulfur protein assembly (CIA) machinery for [4Fe-4S] cluster insertion [PMID:26182403]. It functions in a heterodimer with LTO1/ORAOV1, with deca-GX3 motifs in both proteins mediating their association and the LTO1 C-terminal tryptophan contacting the CIA targeting complex, while YAE1 itself directly recruits the ABCE1 client to form a trimeric LTO1–YAE1–ABCE1 complex [PMID:26182403, PMID:23318452]. By maintaining ABCE1 cluster integrity under aerobic conditions, this complex is required for 60S ribosomal subunit maturation and translation initiation [PMID:23318452]. The adaptor module is functionally conserved: human YAE1D1 and ORAOV1 complement loss of the yeast factors [PMID:26182403, PMID:23318452]. Through its control of ABCE1, the LTO1/YAE1 complex acts upstream in the nonsense-mediated mRNA decay (NMD) pathway, and its loss impairs NMD, derepressing the MHC-I regulators NLRC5, IRF1, and NF-κB and thereby enhancing antigen presentation and T cell-mediated killing of tumor cells [PMID:40987494].","teleology":[{"year":2013,"claim":"Established that Yae1 physically bridges Lto1 and Rli1/ABCE1 into a trimeric complex whose loss disrupts ribosome biogenesis, linking the factor to translation rather than a vague cellular role.","evidence":"Yeast conditional mutants with sucrose-gradient ribosome maturation assays, in vivo/in vitro interaction assays, and human ORAOV1 complementation","pmids":["23318452"],"confidence":"High","gaps":["Did not resolve the molecular basis of how each interaction is configured","Mechanism by which the complex preserves the [4Fe-4S] cluster under aerobic stress not defined at atomic level"]},{"year":2015,"claim":"Defined the molecular logic of the adaptor: it answered how a generic CIA machinery achieves client specificity, showing Yae1-Lto1 act as a dedicated targeting module for apo-Rli1.","evidence":"Protein interaction screens, domain mutagenesis of the Lto1 C-terminal tryptophan and deca-GX3 motifs, Fe-S maturation assays, and cross-species complementation with human YAE1D1","pmids":["26182403"],"confidence":"High","gaps":["No structural model of the assembled complex","Whether other CIA clients use analogous dedicated adaptors not addressed"]},{"year":2025,"claim":"Placed the LTO1/YAE1 complex in a disease-relevant pathway, showing that via ABCE1 it sustains NMD and thereby restrains MHC-I antigen presentation in tumor cells.","evidence":"CRISPR knockouts, fluorescent NMD reporters, polysome profiling, mRNA decay assays, TCR-T/tumor coculture killing, and a mouse tumor model","pmids":["40987494"],"confidence":"High","gaps":["Whether the NMD effect is solely via ABCE1 cluster maturation or involves additional clients","Direct biochemical demonstration that YAE1 loss reduces ABCE1 cluster occupancy in this context not shown"]},{"year":2026,"claim":"Showed the Yae1 domain is a separable, essential functional module by identifying it as a C-terminal domain of S. pombe Tpt1 that can be supplied in trans.","evidence":"Domain deletion/mutagenesis and split-domain genetic complementation in S. pombe growth assays","pmids":["41339091"],"confidence":"Medium","gaps":["Limited to fission yeast; relevance of the Tpt1 fusion arrangement to other organisms unclear","Does not establish whether the fused arrangement confers any functional coupling to RNA 2'-phosphotransferase activity"]},{"year":2016,"claim":"Identified YAE1 as genetically required for tolerance to the antifungal vulpinic acid, but without resolving a direct mechanistic link.","evidence":"Chemical-genetic haploinsufficiency/homozygous profiling, flow cytometry cell cycle analysis, and gene expression measurement in yeast","pmids":["27660105"],"confidence":"Low","gaps":["Single-method chemogenomic screen with no mechanistic connection between YAE1 function and vulpinic acid","Cause of S and G2/M arrest not linked to a defined YAE1 activity"]},{"year":null,"claim":"The atomic structure of the assembled LTO1–YAE1–ABCE1/CIA complex and the precise step at which YAE1 hands apo-ABCE1 to the CIA targeting machinery remain undefined.","evidence":"","pmids":[],"confidence":"High","gaps":["No experimental structure of the trimeric adaptor complex","Whether YAE1 has clients beyond ABCE1 is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[2]}],"complexes":["LTO1-YAE1-ABCE1 adaptor complex"],"partners":["LTO1","ORAOV1","ABCE1","RLI1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NRH1","full_name":"Protein YAE1 homolog","aliases":["Yae1 domain-containing protein 1"],"length_aa":226,"mass_kda":25.3,"function":"The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery (PubMed:26182403). May be required for biogenesis of the large ribosomal subunit and initiation of translation (PubMed:26182403)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9NRH1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/YAE1","classification":"Common Essential","n_dependent_lines":1146,"n_total_lines":1208,"dependency_fraction":0.9486754966887417},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ABCE1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/YAE1","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/YAE1"},"hgnc":{"alias_symbol":["GK003","CIAB2"],"prev_symbol":["C7orf36","YAE1D1"]},"alphafold":{"accession":"Q9NRH1","domains":[{"cath_id":"1.20.1270","chopping":"68-126_200-226","consensus_level":"medium","plddt":86.3086,"start":68,"end":226}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NRH1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NRH1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NRH1-F1-predicted_aligned_error_v6.png","plddt_mean":70.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=YAE1","jax_strain_url":"https://www.jax.org/strain/search?query=YAE1"},"sequence":{"accession":"Q9NRH1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NRH1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NRH1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NRH1"}},"corpus_meta":[{"pmid":"26182403","id":"PMC_26182403","title":"The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion.","date":"2015","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/26182403","citation_count":53,"is_preprint":false},{"pmid":"23318452","id":"PMC_23318452","title":"The function of ORAOV1/LTO1, a gene that is overexpressed frequently in cancer: essential roles in the function and biogenesis of the ribosome.","date":"2013","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/23318452","citation_count":34,"is_preprint":false},{"pmid":"27023521","id":"PMC_27023521","title":"Knock-Down of Endogenous Bornavirus-Like Nucleoprotein 1 Inhibits Cell Growth and Induces Apoptosis in Human Oligodendroglia Cells.","date":"2016","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/27023521","citation_count":23,"is_preprint":false},{"pmid":"15685634","id":"PMC_15685634","title":"Identification of mouse blastocyst genes that are downregulated by double-stranded RNA-mediated knockdown of Oct-4 expression.","date":"2005","source":"Molecular reproduction and development","url":"https://pubmed.ncbi.nlm.nih.gov/15685634","citation_count":16,"is_preprint":false},{"pmid":"31349361","id":"PMC_31349361","title":"Can social support during pregnancy affect maternal DNA methylation? Findings from a cohort of African-Americans.","date":"2019","source":"Pediatric research","url":"https://pubmed.ncbi.nlm.nih.gov/31349361","citation_count":11,"is_preprint":false},{"pmid":"27660105","id":"PMC_27660105","title":"A chemogenomic approach to understand the antifungal action of Lichen-derived vulpinic acid.","date":"2016","source":"Journal of applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27660105","citation_count":7,"is_preprint":false},{"pmid":"36470485","id":"PMC_36470485","title":"In silico analysis of genomic landscape of SARS-CoV-2 and its variant of concerns (Delta and Omicron) reveals changes in the coding potential of miRNAs and their target genes.","date":"2022","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/36470485","citation_count":6,"is_preprint":false},{"pmid":"30556296","id":"PMC_30556296","title":"A case-control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE).","date":"2018","source":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30556296","citation_count":4,"is_preprint":false},{"pmid":"41502527","id":"PMC_41502527","title":"CSRNP1 Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in Hepatocellular Carcinoma.","date":"2025","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/41502527","citation_count":1,"is_preprint":false},{"pmid":"41339091","id":"PMC_41339091","title":"Fission yeast Tpt1 is composed of tandem RNA 2'-phosphotransferase and Yae1 domains, both of which are essential for viability.","date":"2026","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/41339091","citation_count":0,"is_preprint":false},{"pmid":"40987494","id":"PMC_40987494","title":"LTO1 and YAE1 regulate MHC-I expression via nonsense-mediated RNA decay in tumor cells.","date":"2025","source":"Journal for immunotherapy of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/40987494","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.06.25327057","title":"Identification of (ultra-)rare functional promoter mutations in cancer using sequence-based deep learning models","date":"2025-05-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.06.25327057","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9038,"output_tokens":1663,"usd":0.02603,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8443,"output_tokens":2143,"usd":0.047895,"stage2_stop_reason":"end_turn"},"total_usd":0.073925,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"Yae1 and Lto1 form a complex that functions as a target-specific adaptor recruiting apo-Rli1 to the generic CIA (cytosolic Fe-S protein assembly) machinery for iron-sulfur cluster insertion. Lto1 uses its conserved C-terminal tryptophan to bind the CIA targeting complex, deca-GX3 motifs in both Yae1 and Lto1 mediate their complex formation, and Yae1 directly recruits Rli1. Human YAE1D1 can replace yeast Yae1, demonstrating evolutionary conservation.\",\n      \"method\": \"Systematic protein interaction approaches (Co-IP/pulldown), yeast depletion/complementation experiments, domain mutagenesis (C-terminal tryptophan, deca-GX3 motifs), Fe-S cluster maturation assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (protein interaction screens, mutagenesis of specific motifs, functional Fe-S maturation assays, cross-species complementation) in a single rigorous study\",\n      \"pmids\": [\"26182403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Yae1 bridges the interaction between Lto1 (YNL260c/ORAOV1) and Rli1/ABCE1, forming a trimeric complex. Loss of Lto1 (and by extension this complex) leads to defective 60S ribosomal subunit maturation and abrogated translation initiation. The complex is required for maintaining Rli1/ABCE1 [4Fe-4S] cluster integrity under aerobic conditions. Interactions were demonstrated both in vivo and in vitro.\",\n      \"method\": \"Yeast conditional mutants, ribosome maturation assays (sucrose gradient fractionation), in vivo and in vitro protein interaction assays (Co-IP, pulldown), genetic complementation with human ORAOV1\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal in vivo and in vitro interaction assays, functional ribosome biogenesis readouts, cross-species complementation, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"23318452\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The LTO1/YAE1 complex regulates nonsense-mediated RNA decay (NMD) and MHC-I antigen presentation in tumor cells. Deficiency of LTO1, YAE1, or their downstream target ABCE1 impairs NMD, causing overexpression of MHC-I regulators NLRC5, IRF1, and NF-κB, resulting in enhanced T cell activation and tumor cell killing. The complex acts upstream of ABCE1 in the NMD pathway.\",\n      \"method\": \"CRISPR/Cas9 knockouts, overexpression, mutational analysis, fluorescent NMD reporter assays, FACS, RT-qPCR, mRNA decay assays, polysome profiling, TCR-T cell/tumor coculture killing assays, mouse tumor model\",\n      \"journal\": \"Journal for immunotherapy of cancer\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (CRISPR KO, reporter assays, polysome profiling, in vivo mouse model) in a single study establishing pathway placement upstream of ABCE1/NMD\",\n      \"pmids\": [\"40987494\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In fission yeast Schizosaccharomyces pombe, Tpt1 contains a C-terminal domain (aa 238-365) homologous to budding yeast iron-sulfur cluster assembly factor Yae1. Both the RNA 2'-phosphotransferase catalytic domain and the C-terminal Yae1 domain of SpTpt1 are essential for S. pombe growth, though they need not be covalently linked within the same polypeptide. This identifies the Yae1 domain as a functionally essential, separable module.\",\n      \"method\": \"Domain deletion/mutational analysis, genetic complementation (split-domain rescue), S. pombe growth assays, sequence homology analysis\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic complementation and mutagenesis in a single study establishing essential nature of the Yae1 domain in fission yeast, but single lab and limited to this organism context\",\n      \"pmids\": [\"41339091\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Yeast strains lacking YAE1 are hypersensitive to the antifungal compound vulpinic acid, and vulpinic acid treatment significantly lowers YAE1 expression; cell cycle arrest in S and G2/M phases is observed under these conditions.\",\n      \"method\": \"Haploinsufficiency and homozygous-profiling chemical-genetic assays, flow cytometry cell cycle analysis, relative gene expression measurement\",\n      \"journal\": \"Journal of applied microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — chemogenomic sensitivity screen with single-method validation; establishes genetic requirement for YAE1 under vulpinic acid stress but provides no direct mechanistic insight into YAE1 function\",\n      \"pmids\": [\"27660105\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"YAE1 (human YAE1D1) forms a conserved adaptor complex with LTO1/ORAOV1 that recruits apo-ABCE1/Rli1 to the CIA machinery for iron-sulfur cluster insertion via a chain of binding events (LTO1 C-terminal tryptophan contacts the CIA targeting complex, deca-GX3 motifs mediate Yae1-Lto1 heterodimerization, and Yae1 directly recruits ABCE1); this complex is required for 60S ribosome biogenesis, translation initiation, and—by enabling ABCE1 function—also suppresses nonsense-mediated mRNA decay and thereby dampens MHC-I antigen presentation in tumor cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"YAE1 (human YAE1D1) is a target-specific adaptor that delivers apo-ABCE1/Rli1 to the cytosolic iron-sulfur protein assembly (CIA) machinery for [4Fe-4S] cluster insertion [#0]. It functions in a heterodimer with LTO1/ORAOV1, with deca-GX3 motifs in both proteins mediating their association and the LTO1 C-terminal tryptophan contacting the CIA targeting complex, while YAE1 itself directly recruits the ABCE1 client to form a trimeric LTO1–YAE1–ABCE1 complex [#0, #1]. By maintaining ABCE1 cluster integrity under aerobic conditions, this complex is required for 60S ribosomal subunit maturation and translation initiation [#1]. The adaptor module is functionally conserved: human YAE1D1 and ORAOV1 complement loss of the yeast factors [#0, #1]. Through its control of ABCE1, the LTO1/YAE1 complex acts upstream in the nonsense-mediated mRNA decay (NMD) pathway, and its loss impairs NMD, derepressing the MHC-I regulators NLRC5, IRF1, and NF-κB and thereby enhancing antigen presentation and T cell-mediated killing of tumor cells [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that Yae1 physically bridges Lto1 and Rli1/ABCE1 into a trimeric complex whose loss disrupts ribosome biogenesis, linking the factor to translation rather than a vague cellular role.\",\n      \"evidence\": \"Yeast conditional mutants with sucrose-gradient ribosome maturation assays, in vivo/in vitro interaction assays, and human ORAOV1 complementation\",\n      \"pmids\": [\"23318452\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the molecular basis of how each interaction is configured\", \"Mechanism by which the complex preserves the [4Fe-4S] cluster under aerobic stress not defined at atomic level\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined the molecular logic of the adaptor: it answered how a generic CIA machinery achieves client specificity, showing Yae1-Lto1 act as a dedicated targeting module for apo-Rli1.\",\n      \"evidence\": \"Protein interaction screens, domain mutagenesis of the Lto1 C-terminal tryptophan and deca-GX3 motifs, Fe-S maturation assays, and cross-species complementation with human YAE1D1\",\n      \"pmids\": [\"26182403\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of the assembled complex\", \"Whether other CIA clients use analogous dedicated adaptors not addressed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed the LTO1/YAE1 complex in a disease-relevant pathway, showing that via ABCE1 it sustains NMD and thereby restrains MHC-I antigen presentation in tumor cells.\",\n      \"evidence\": \"CRISPR knockouts, fluorescent NMD reporters, polysome profiling, mRNA decay assays, TCR-T/tumor coculture killing, and a mouse tumor model\",\n      \"pmids\": [\"40987494\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the NMD effect is solely via ABCE1 cluster maturation or involves additional clients\", \"Direct biochemical demonstration that YAE1 loss reduces ABCE1 cluster occupancy in this context not shown\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Showed the Yae1 domain is a separable, essential functional module by identifying it as a C-terminal domain of S. pombe Tpt1 that can be supplied in trans.\",\n      \"evidence\": \"Domain deletion/mutagenesis and split-domain genetic complementation in S. pombe growth assays\",\n      \"pmids\": [\"41339091\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Limited to fission yeast; relevance of the Tpt1 fusion arrangement to other organisms unclear\", \"Does not establish whether the fused arrangement confers any functional coupling to RNA 2'-phosphotransferase activity\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified YAE1 as genetically required for tolerance to the antifungal vulpinic acid, but without resolving a direct mechanistic link.\",\n      \"evidence\": \"Chemical-genetic haploinsufficiency/homozygous profiling, flow cytometry cell cycle analysis, and gene expression measurement in yeast\",\n      \"pmids\": [\"27660105\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single-method chemogenomic screen with no mechanistic connection between YAE1 function and vulpinic acid\", \"Cause of S and G2/M arrest not linked to a defined YAE1 activity\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The atomic structure of the assembled LTO1–YAE1–ABCE1/CIA complex and the precise step at which YAE1 hands apo-ABCE1 to the CIA targeting machinery remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No experimental structure of the trimeric adaptor complex\", \"Whether YAE1 has clients beyond ABCE1 is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"LTO1-YAE1-ABCE1 adaptor complex\"],\n    \"partners\": [\"LTO1\", \"ORAOV1\", \"ABCE1\", \"RLI1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}