{"gene":"MRPL20","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":1990,"finding":"MRP-L20 (yeast ortholog of MRPL20) encodes a 22.3-kDa mitochondrial ribosomal large subunit protein with an N-terminal presequence of 18 amino acids. Gene disruption experiments showed that the YmL20 protein is essential for mitochondrial function, and its absence causes instability of mitochondrial DNA.","method":"Gene cloning, sequencing, Southern blot hybridization, gene disruption experiments","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gene disruption with defined mitochondrial phenotype in yeast ortholog, single lab but multiple methods","pmids":["2183197"],"is_preprint":false},{"year":2025,"finding":"Copper stress reduces OXA1L levels in mitochondria, which disrupts MRPL20 import into mitochondria and impairs oxidative phosphorylation complex I synthesis. This mitochondrial dysfunction promotes MRPL20 nuclear translocation, which triggers the mitochondrial unfolded protein response (UPRmt) as an adaptive mechanism to restore mitochondrial proteostasis during early cuproptosis.","method":"Spatio-temporal mass spectrometry (STMS) of subcellular proteome dynamics, genetic functional screen, subcellular fractionation/localization tracking","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — novel multi-method approach (proteomics + genetic screen) in a single preprint lab, not yet peer-reviewed or replicated","pmids":["bio_10.1101_2025.07.01.662679"],"is_preprint":true}],"current_model":"MRPL20 is a mitochondrial ribosomal large subunit protein whose import into mitochondria depends on OXA1L; under copper stress, reduced OXA1L disrupts MRPL20 import and impairs oxidative phosphorylation complex I assembly, while mislocalized MRPL20 undergoes nuclear translocation to trigger the mitochondrial unfolded protein response, and loss of the yeast ortholog (YmL20) causes mitochondrial dysfunction and mitochondrial DNA instability."},"narrative":{"mechanistic_narrative":"MRPL20 is a structural protein of the mitochondrial large ribosomal subunit required for mitochondrial translation and genome maintenance, established through its essential yeast ortholog YmL20, whose disruption causes mitochondrial dysfunction and mitochondrial DNA instability [PMID:2183197]. Its mitochondrial import depends on OXA1L: under copper stress, OXA1L levels fall, MRPL20 import is disrupted, and oxidative phosphorylation complex I synthesis is impaired; mislocalized MRPL20 translocates to the nucleus and triggers the mitochondrial unfolded protein response as an adaptive response during early cuproptosis [PMID:bio_10.1101_2025.07.01.662679]. Beyond these findings, the structural role of MRPL20 within the assembled ribosome and the mechanism of its nuclear signaling are not characterized in the available corpus.","teleology":[{"year":1990,"claim":"Established that MRPL20's ortholog encodes a large-subunit mitochondrial ribosomal protein essential for mitochondrial function, linking it for the first time to maintenance of the mitochondrial genome.","evidence":"Gene cloning, sequencing, and disruption of the yeast ortholog YmL20 with phenotypic analysis","pmids":["2183197"],"confidence":"Medium","gaps":["Human MRPL20 function inferred only from yeast ortholog","Direct demonstration of incorporation into the ribosome not shown","Mechanism connecting loss to mtDNA instability unresolved"]},{"year":2025,"claim":"Connected MRPL20 to copper stress biology by showing its mitochondrial import depends on OXA1L and that mislocalization drives a nuclear UPRmt signal, defining a stress-responsive role beyond constitutive ribosome function.","evidence":"Spatio-temporal mass spectrometry, genetic functional screen, and subcellular fractionation in a copper-stress/cuproptosis model (preprint)","pmids":["bio_10.1101_2025.07.01.662679"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed or independently replicated","Mechanism by which nuclear MRPL20 triggers UPRmt not defined","Direct OXA1L–MRPL20 interaction during import not demonstrated"]},{"year":null,"claim":"How MRPL20 is positioned within the assembled mitochondrial large ribosomal subunit and how its nuclear translocation is sensed to activate the UPRmt remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of MRPL20 within the ribosome in the corpus","Signaling effectors downstream of nuclear MRPL20 unknown","Human-specific phenotypes of MRPL20 loss not characterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[1]}],"complexes":["mitochondrial large ribosomal subunit"],"partners":["OXA1L"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BYC9","full_name":"Large ribosomal subunit protein bL20m","aliases":["39S ribosomal protein L20, mitochondrial","L20mt","MRP-L20"],"length_aa":149,"mass_kda":17.4,"function":"","subcellular_location":"Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q9BYC9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MRPL20","classification":"Not Classified","n_dependent_lines":503,"n_total_lines":1208,"dependency_fraction":0.4163907284768212},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CTPS1","stoichiometry":0.2},{"gene":"IPO5","stoichiometry":0.2},{"gene":"LSM14A","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2},{"gene":"PSME3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MRPL20","total_profiled":1310},"omim":[{"mim_id":"611833","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L20; MRPL20","url":"https://www.omim.org/entry/611833"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Mitochondria","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MRPL20"},"hgnc":{"alias_symbol":["FLJ10024","bL20m"],"prev_symbol":[]},"alphafold":{"accession":"Q9BYC9","domains":[{"cath_id":"1.10.1900.20","chopping":"68-132","consensus_level":"medium","plddt":96.1955,"start":68,"end":132}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BYC9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BYC9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BYC9-F1-predicted_aligned_error_v6.png","plddt_mean":91.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MRPL20","jax_strain_url":"https://www.jax.org/strain/search?query=MRPL20"},"sequence":{"accession":"Q9BYC9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BYC9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BYC9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BYC9"}},"corpus_meta":[{"pmid":"24098497","id":"PMC_24098497","title":"Concurrent gene signatures for han chinese breast cancers.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24098497","citation_count":67,"is_preprint":false},{"pmid":"2183197","id":"PMC_2183197","title":"Cloning and characterization of nuclear genes for two mitochondrial ribosomal proteins in Saccharomyces cerevisiae.","date":"1990","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2183197","citation_count":40,"is_preprint":false},{"pmid":"8203164","id":"PMC_8203164","title":"The complete sequence of an 18,002 bp segment of Saccharomyces cerevisiae chromosome XI contains the HBS1, MRP-L20 and PRP16 genes, and six new open reading frames.","date":"1994","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/8203164","citation_count":12,"is_preprint":false},{"pmid":"35988669","id":"PMC_35988669","title":"The lncRNA MRPL20-AS1 is associated with severe OSAS and downregulated upon hypoxic injury of endothelial cells.","date":"2022","source":"International journal of cardiology","url":"https://pubmed.ncbi.nlm.nih.gov/35988669","citation_count":10,"is_preprint":false},{"pmid":"36824437","id":"PMC_36824437","title":"Integrated genomic analysis defines molecular subgroups in dilated cardiomyopathy and identifies novel biomarkers based on machine learning methods.","date":"2023","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36824437","citation_count":2,"is_preprint":false},{"pmid":"39529627","id":"PMC_39529627","title":"The impact of hsa-miR-1972 on the expression of von Willebrand factor in breast cancer progression regulation.","date":"2024","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/39529627","citation_count":1,"is_preprint":false},{"pmid":"41749276","id":"PMC_41749276","title":"Interplay of the nasal microbiome and epigenome among adolescents.","date":"2026","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/41749276","citation_count":0,"is_preprint":false},{"pmid":"1481572","id":"PMC_1481572","title":"Mapping the putative RNA helicase genes by sequence overlapping.","date":"1992","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/1481572","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.01.662679","title":"Spatio-temporal mass spectrometry in living cells reveals regulators of cuproptosis","date":"2025-07-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.01.662679","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6675,"output_tokens":612,"usd":0.014602,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6990,"output_tokens":1377,"usd":0.034688,"stage2_stop_reason":"end_turn"},"total_usd":0.04929,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1990,\n      \"finding\": \"MRP-L20 (yeast ortholog of MRPL20) encodes a 22.3-kDa mitochondrial ribosomal large subunit protein with an N-terminal presequence of 18 amino acids. Gene disruption experiments showed that the YmL20 protein is essential for mitochondrial function, and its absence causes instability of mitochondrial DNA.\",\n      \"method\": \"Gene cloning, sequencing, Southern blot hybridization, gene disruption experiments\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gene disruption with defined mitochondrial phenotype in yeast ortholog, single lab but multiple methods\",\n      \"pmids\": [\"2183197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Copper stress reduces OXA1L levels in mitochondria, which disrupts MRPL20 import into mitochondria and impairs oxidative phosphorylation complex I synthesis. This mitochondrial dysfunction promotes MRPL20 nuclear translocation, which triggers the mitochondrial unfolded protein response (UPRmt) as an adaptive mechanism to restore mitochondrial proteostasis during early cuproptosis.\",\n      \"method\": \"Spatio-temporal mass spectrometry (STMS) of subcellular proteome dynamics, genetic functional screen, subcellular fractionation/localization tracking\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — novel multi-method approach (proteomics + genetic screen) in a single preprint lab, not yet peer-reviewed or replicated\",\n      \"pmids\": [\"bio_10.1101_2025.07.01.662679\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"MRPL20 is a mitochondrial ribosomal large subunit protein whose import into mitochondria depends on OXA1L; under copper stress, reduced OXA1L disrupts MRPL20 import and impairs oxidative phosphorylation complex I assembly, while mislocalized MRPL20 undergoes nuclear translocation to trigger the mitochondrial unfolded protein response, and loss of the yeast ortholog (YmL20) causes mitochondrial dysfunction and mitochondrial DNA instability.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPL20 is a structural protein of the mitochondrial large ribosomal subunit required for mitochondrial translation and genome maintenance, established through its essential yeast ortholog YmL20, whose disruption causes mitochondrial dysfunction and mitochondrial DNA instability [#0]. Its mitochondrial import depends on OXA1L: under copper stress, OXA1L levels fall, MRPL20 import is disrupted, and oxidative phosphorylation complex I synthesis is impaired; mislocalized MRPL20 translocates to the nucleus and triggers the mitochondrial unfolded protein response as an adaptive response during early cuproptosis [#1]. Beyond these findings, the structural role of MRPL20 within the assembled ribosome and the mechanism of its nuclear signaling are not characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Established that MRPL20's ortholog encodes a large-subunit mitochondrial ribosomal protein essential for mitochondrial function, linking it for the first time to maintenance of the mitochondrial genome.\",\n      \"evidence\": \"Gene cloning, sequencing, and disruption of the yeast ortholog YmL20 with phenotypic analysis\",\n      \"pmids\": [\"2183197\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Human MRPL20 function inferred only from yeast ortholog\",\n        \"Direct demonstration of incorporation into the ribosome not shown\",\n        \"Mechanism connecting loss to mtDNA instability unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected MRPL20 to copper stress biology by showing its mitochondrial import depends on OXA1L and that mislocalization drives a nuclear UPRmt signal, defining a stress-responsive role beyond constitutive ribosome function.\",\n      \"evidence\": \"Spatio-temporal mass spectrometry, genetic functional screen, and subcellular fractionation in a copper-stress/cuproptosis model (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.07.01.662679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint, not peer-reviewed or independently replicated\",\n        \"Mechanism by which nuclear MRPL20 triggers UPRmt not defined\",\n        \"Direct OXA1L–MRPL20 interaction during import not demonstrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MRPL20 is positioned within the assembled mitochondrial large ribosomal subunit and how its nuclear translocation is sensed to activate the UPRmt remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of MRPL20 within the ribosome in the corpus\",\n        \"Signaling effectors downstream of nuclear MRPL20 unknown\",\n        \"Human-specific phenotypes of MRPL20 loss not characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"mitochondrial large ribosomal subunit\"],\n    \"partners\": [\"OXA1L\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":1,"faith_pct":100.0}}