{"gene":"RPP40","run_date":"2026-06-10T07:46:27","timeline":{"discoveries":[{"year":1998,"finding":"Rpp40 co-purifies with catalytically active human RNase P holoenzyme; polyclonal antibodies against recombinant Rpp40 precipitate active holoenzyme, establishing it as a bona fide protein subunit of the tRNA-processing ribonucleoprotein.","method":"Co-purification, immunoprecipitation of active holoenzyme with polyclonal antibodies against recombinant Rpp40","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal immunoprecipitation of active enzyme, replicated in subsequent independent studies","pmids":["9630247"],"is_preprint":false},{"year":1999,"finding":"Rpp40 is confirmed as one of at least eight protein subunits of human RNase P in HeLa cells; antibodies against Rpp40 precipitate catalytically active RNase P.","method":"Immunoprecipitation of catalytically active RNase P from HeLa cell extracts","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Strong — independently confirmed across multiple labs using immunoprecipitation of active enzyme","pmids":["10024167"],"is_preprint":false},{"year":2001,"finding":"Rpp40 participates in extensive but weak protein-protein interactions with other subunits (hpop1, Rpp21, Rpp29, Rpp30, Rpp38) within the human nuclear RNase P holoenzyme complex, as detected by yeast two-hybrid analysis.","method":"Yeast two-hybrid system","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single yeast two-hybrid screen, no orthogonal validation of Rpp40-specific interactions reported","pmids":["11158571"],"is_preprint":false},{"year":2004,"finding":"Rpp40 directly interacts with specific protein subunits and RNA regions within the human RNase MRP complex; GST pull-down experiments identified direct protein-protein and protein-RNA interactions involving Rpp40, contributing to a structural model of RNase MRP assembly.","method":"GST pull-down assays; mutant RNase MRP RNA analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — GST pull-down with mutant RNA analysis, multiple interactions mapped in a single systematic study","pmids":["15096576"],"is_preprint":false},{"year":2006,"finding":"Rpp40 sediments in both 12S and 60–80S fractions by glycerol gradient sedimentation, and co-immunoprecipitation shows it associates with both RNase MRP and RNase P complexes; it is likely present in all RNase MRP particles (not just a subset), in contrast to subunits such as Rpp20 and Rpp25.","method":"Glycerol gradient sedimentation; co-immunoprecipitation with VSV-epitope-tagged subunits","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal biochemical methods (sedimentation + co-IP) in a single systematic study","pmids":["16723659"],"is_preprint":false},{"year":2025,"finding":"RPP40 knockdown or overexpression in HCC cells demonstrates that RPP40 promotes cell proliferation, migration, and invasion, and coordinates transcription of pre-rRNA and expression of ribosomal protein genes to drive HCC malignancy.","method":"Loss-of-function and gain-of-function cellular assays (proliferation, migration, invasion); transcriptional analysis of rRNA and ribosomal protein genes in HCC cell lines","journal":"Gene","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, functional cellular assays without mechanistic reconstitution or structural validation; abstract does not detail orthogonal methods","pmids":["40517827"],"is_preprint":false}],"current_model":"RPP40 is a core protein subunit of both human RNase P and RNase MRP ribonucleoprotein complexes, engaging in direct protein-protein and protein-RNA interactions required for holoenzyme assembly; it associates with essentially all RNase MRP particles and contributes to pre-tRNA and pre-rRNA processing, and in a cancer-cell context has been shown to coordinate pre-rRNA transcription and ribosomal protein gene expression to promote cell proliferation and invasion."},"narrative":{"mechanistic_narrative":"RPP40 is a core protein subunit of the human RNase P ribonucleoprotein, co-purifying with catalytically active holoenzyme and being precipitated together with active enzyme by anti-RPP40 antibodies, which established it as one of at least eight protein subunits of the tRNA-processing complex [PMID:9630247, PMID:10024167]. RPP40 is shared between RNase P and the related RNase MRP complex: it sediments in both small (12S) and large (60–80S) particles and co-immunoprecipitates with both holoenzymes, and unlike subunits such as Rpp20 and Rpp25 it associates with essentially all RNase MRP particles [PMID:16723659]. Within RNase MRP it makes direct protein-protein and protein-RNA contacts that contribute to a structural model of complex assembly [PMID:15096576]. Beyond these assembly and processing roles, RPP40 has been linked in hepatocellular carcinoma cells to coordination of pre-rRNA transcription and ribosomal protein gene expression promoting proliferation and invasion [PMID:40517827].","teleology":[{"year":1998,"claim":"Established whether RPP40 is a genuine constituent of the tRNA-processing machinery rather than a co-incidental copurifying protein, by tying it directly to catalytic activity.","evidence":"Co-purification and immunoprecipitation of active RNase P holoenzyme using antibodies against recombinant Rpp40","pmids":["9630247"],"confidence":"Medium","gaps":["Does not define RPP40's specific molecular contribution to catalysis or substrate binding","No structural localization within the complex"]},{"year":1999,"claim":"Confirmed RPP40 as a stable subunit of the multi-protein human RNase P enzyme across independent preparations.","evidence":"Immunoprecipitation of catalytically active RNase P from HeLa extracts","pmids":["10024167"],"confidence":"Medium","gaps":["Subunit stoichiometry not resolved","Role in enzyme function not addressed"]},{"year":2001,"claim":"Mapped RPP40 into the holoenzyme interaction network, defining which other subunits it contacts during assembly.","evidence":"Yeast two-hybrid analysis of human nuclear RNase P subunits","pmids":["11158571"],"confidence":"Low","gaps":["Single yeast two-hybrid screen with no orthogonal validation of RPP40-specific interactions","Interactions described as weak; in vivo relevance unconfirmed"]},{"year":2004,"claim":"Extended RPP40 beyond RNase P by mapping its direct protein and RNA contacts within RNase MRP, contributing to an assembly model.","evidence":"GST pull-down assays and analysis of mutant RNase MRP RNA","pmids":["15096576"],"confidence":"Medium","gaps":["Precise RNA-binding determinants on RPP40 not defined at residue level","No high-resolution structure of the assembled complex"]},{"year":2006,"claim":"Distinguished RPP40's distribution across particle populations, showing it is present in essentially all RNase MRP particles in contrast to substoichiometric subunits.","evidence":"Glycerol gradient sedimentation and co-immunoprecipitation with VSV-tagged subunits","pmids":["16723659"],"confidence":"Medium","gaps":["Functional consequence of pan-particle association not tested","Does not address pre-rRNA processing activity directly"]},{"year":2025,"claim":"Probed a cellular-phenotype role for RPP40, linking it to pre-rRNA transcription and ribosomal protein gene expression that drive cancer-cell proliferation and invasion.","evidence":"Loss- and gain-of-function proliferation/migration/invasion assays and transcriptional analysis in HCC cell lines","pmids":["40517827"],"confidence":"Low","gaps":["Single lab, no mechanistic reconstitution or structural validation","Direct molecular link between RNase P/MRP function and rRNA transcription program not established","Causality versus correlation in transcriptional changes unresolved"]},{"year":null,"claim":"How RPP40's specific subunit contacts contribute to RNase P/MRP catalysis and substrate selection, and the molecular basis of its reported influence on rRNA transcription, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure assigning RPP40 a defined catalytic or substrate-positioning role","Mechanism connecting RNase MRP subunit identity to pre-rRNA transcriptional output not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[3]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,3]}],"complexes":["RNase P","RNase MRP"],"partners":["POP1","RPP21","RPP29","RPP30","RPP38"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O75818","full_name":"Ribonuclease P protein subunit p40","aliases":["RNase P subunit 1"],"length_aa":363,"mass_kda":41.8,"function":"Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:30454648, PubMed:9630247). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465)","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/O75818/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPP40","classification":"Common Essential","n_dependent_lines":1161,"n_total_lines":1208,"dependency_fraction":0.9610927152317881},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"RPP30","stoichiometry":10.0},{"gene":"NPM1","stoichiometry":0.2},{"gene":"RACK1","stoichiometry":0.2},{"gene":"SSB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RPP40","total_profiled":1310},"omim":[{"mim_id":"606117","title":"RIBONUCLEASE P/MRP SUBUNIT p40; RPP40","url":"https://www.omim.org/entry/606117"},{"mim_id":"606116","title":"RIBONUCLEASE P/MRP SUBUNIT p38; RPP38","url":"https://www.omim.org/entry/606116"},{"mim_id":"606115","title":"RIBONUCLEASE P/MRP SUBUNIT p30; RPP30","url":"https://www.omim.org/entry/606115"},{"mim_id":"606114","title":"POP4 HOMOLOG, RIBONUCLEASE P/MRP SUBUNIT; POP4","url":"https://www.omim.org/entry/606114"},{"mim_id":"606113","title":"POP7 HOMOLOG, RIBONUCLEASE P/MRP SUBUNIT; POP7","url":"https://www.omim.org/entry/606113"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPP40"},"hgnc":{"alias_symbol":["bA428J1.3"],"prev_symbol":["RNASEP1"]},"alphafold":{"accession":"O75818","domains":[{"cath_id":"-","chopping":"2-65_209-357","consensus_level":"high","plddt":90.9973,"start":2,"end":357},{"cath_id":"-","chopping":"67-206","consensus_level":"high","plddt":93.2815,"start":67,"end":206}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75818","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75818-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75818-F1-predicted_aligned_error_v6.png","plddt_mean":91.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPP40","jax_strain_url":"https://www.jax.org/strain/search?query=RPP40"},"sequence":{"accession":"O75818","fasta_url":"https://rest.uniprot.org/uniprotkb/O75818.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75818/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75818"}},"corpus_meta":[{"pmid":"15096576","id":"PMC_15096576","title":"Mutual interactions between subunits of the human RNase MRP ribonucleoprotein complex.","date":"2004","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/15096576","citation_count":86,"is_preprint":false},{"pmid":"9630247","id":"PMC_9630247","title":"Autoantigenic properties of some protein subunits of catalytically active complexes of human ribonuclease P.","date":"1998","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/9630247","citation_count":52,"is_preprint":false},{"pmid":"11158571","id":"PMC_11158571","title":"Protein-protein interactions with subunits of human nuclear RNase P.","date":"2001","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11158571","citation_count":51,"is_preprint":false},{"pmid":"10024167","id":"PMC_10024167","title":"Rpp14 and Rpp29, two protein subunits of human ribonuclease P.","date":"1999","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/10024167","citation_count":48,"is_preprint":false},{"pmid":"12003489","id":"PMC_12003489","title":"Purification and characterization of Rpp25, an RNA-binding protein subunit of human ribonuclease P.","date":"2002","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/12003489","citation_count":47,"is_preprint":false},{"pmid":"16723659","id":"PMC_16723659","title":"Differential association of protein subunits with the human RNase MRP and RNase P complexes.","date":"2006","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/16723659","citation_count":44,"is_preprint":false},{"pmid":"32512867","id":"PMC_32512867","title":"The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles.","date":"2020","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/32512867","citation_count":42,"is_preprint":false},{"pmid":"24528495","id":"PMC_24528495","title":"An immunohistochemical analysis of a newly developed, mouse monoclonal p40 (BC28) antibody in lung, bladder, skin, breast, prostate, and head and neck cancers.","date":"2014","source":"Archives of pathology & laboratory medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24528495","citation_count":31,"is_preprint":false},{"pmid":"36977152","id":"PMC_36977152","title":"Effect of Demographics and Time to Sample Processing on the qPCR Detection of Pathogenic Leptospira spp. from Human Samples in the National Reference Laboratory for Leptospirosis, Brazil.","date":"2023","source":"Tropical medicine and infectious disease","url":"https://pubmed.ncbi.nlm.nih.gov/36977152","citation_count":3,"is_preprint":false},{"pmid":"40517827","id":"PMC_40517827","title":"Ribonuclease P/MRP subunit RPP40 coordinates the transcription of pre-rRNA and ribosomal protein genes to promote Hepatocellular carcinoma malignancy.","date":"2025","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/40517827","citation_count":1,"is_preprint":false},{"pmid":"41933259","id":"PMC_41933259","title":"Comprehensive profiling of RPP40 across human cancers reveals its essential role and multidimensional clinical correlates.","date":"2026","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41933259","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7002,"output_tokens":1342,"usd":0.020568,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8013,"output_tokens":2021,"usd":0.045295,"stage2_stop_reason":"end_turn"},"total_usd":0.065863,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"Rpp40 co-purifies with catalytically active human RNase P holoenzyme; polyclonal antibodies against recombinant Rpp40 precipitate active holoenzyme, establishing it as a bona fide protein subunit of the tRNA-processing ribonucleoprotein.\",\n      \"method\": \"Co-purification, immunoprecipitation of active holoenzyme with polyclonal antibodies against recombinant Rpp40\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal immunoprecipitation of active enzyme, replicated in subsequent independent studies\",\n      \"pmids\": [\"9630247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Rpp40 is confirmed as one of at least eight protein subunits of human RNase P in HeLa cells; antibodies against Rpp40 precipitate catalytically active RNase P.\",\n      \"method\": \"Immunoprecipitation of catalytically active RNase P from HeLa cell extracts\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independently confirmed across multiple labs using immunoprecipitation of active enzyme\",\n      \"pmids\": [\"10024167\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Rpp40 participates in extensive but weak protein-protein interactions with other subunits (hpop1, Rpp21, Rpp29, Rpp30, Rpp38) within the human nuclear RNase P holoenzyme complex, as detected by yeast two-hybrid analysis.\",\n      \"method\": \"Yeast two-hybrid system\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single yeast two-hybrid screen, no orthogonal validation of Rpp40-specific interactions reported\",\n      \"pmids\": [\"11158571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Rpp40 directly interacts with specific protein subunits and RNA regions within the human RNase MRP complex; GST pull-down experiments identified direct protein-protein and protein-RNA interactions involving Rpp40, contributing to a structural model of RNase MRP assembly.\",\n      \"method\": \"GST pull-down assays; mutant RNase MRP RNA analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — GST pull-down with mutant RNA analysis, multiple interactions mapped in a single systematic study\",\n      \"pmids\": [\"15096576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Rpp40 sediments in both 12S and 60–80S fractions by glycerol gradient sedimentation, and co-immunoprecipitation shows it associates with both RNase MRP and RNase P complexes; it is likely present in all RNase MRP particles (not just a subset), in contrast to subunits such as Rpp20 and Rpp25.\",\n      \"method\": \"Glycerol gradient sedimentation; co-immunoprecipitation with VSV-epitope-tagged subunits\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal biochemical methods (sedimentation + co-IP) in a single systematic study\",\n      \"pmids\": [\"16723659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RPP40 knockdown or overexpression in HCC cells demonstrates that RPP40 promotes cell proliferation, migration, and invasion, and coordinates transcription of pre-rRNA and expression of ribosomal protein genes to drive HCC malignancy.\",\n      \"method\": \"Loss-of-function and gain-of-function cellular assays (proliferation, migration, invasion); transcriptional analysis of rRNA and ribosomal protein genes in HCC cell lines\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, functional cellular assays without mechanistic reconstitution or structural validation; abstract does not detail orthogonal methods\",\n      \"pmids\": [\"40517827\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPP40 is a core protein subunit of both human RNase P and RNase MRP ribonucleoprotein complexes, engaging in direct protein-protein and protein-RNA interactions required for holoenzyme assembly; it associates with essentially all RNase MRP particles and contributes to pre-tRNA and pre-rRNA processing, and in a cancer-cell context has been shown to coordinate pre-rRNA transcription and ribosomal protein gene expression to promote cell proliferation and invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPP40 is a core protein subunit of the human RNase P ribonucleoprotein, co-purifying with catalytically active holoenzyme and being precipitated together with active enzyme by anti-RPP40 antibodies, which established it as one of at least eight protein subunits of the tRNA-processing complex [#0, #1]. RPP40 is shared between RNase P and the related RNase MRP complex: it sediments in both small (12S) and large (60–80S) particles and co-immunoprecipitates with both holoenzymes, and unlike subunits such as Rpp20 and Rpp25 it associates with essentially all RNase MRP particles [#4]. Within RNase MRP it makes direct protein-protein and protein-RNA contacts that contribute to a structural model of complex assembly [#3]. Beyond these assembly and processing roles, RPP40 has been linked in hepatocellular carcinoma cells to coordination of pre-rRNA transcription and ribosomal protein gene expression promoting proliferation and invasion [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established whether RPP40 is a genuine constituent of the tRNA-processing machinery rather than a co-incidental copurifying protein, by tying it directly to catalytic activity.\",\n      \"evidence\": \"Co-purification and immunoprecipitation of active RNase P holoenzyme using antibodies against recombinant Rpp40\",\n      \"pmids\": [\"9630247\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not define RPP40's specific molecular contribution to catalysis or substrate binding\", \"No structural localization within the complex\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Confirmed RPP40 as a stable subunit of the multi-protein human RNase P enzyme across independent preparations.\",\n      \"evidence\": \"Immunoprecipitation of catalytically active RNase P from HeLa extracts\",\n      \"pmids\": [\"10024167\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Subunit stoichiometry not resolved\", \"Role in enzyme function not addressed\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Mapped RPP40 into the holoenzyme interaction network, defining which other subunits it contacts during assembly.\",\n      \"evidence\": \"Yeast two-hybrid analysis of human nuclear RNase P subunits\",\n      \"pmids\": [\"11158571\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single yeast two-hybrid screen with no orthogonal validation of RPP40-specific interactions\", \"Interactions described as weak; in vivo relevance unconfirmed\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Extended RPP40 beyond RNase P by mapping its direct protein and RNA contacts within RNase MRP, contributing to an assembly model.\",\n      \"evidence\": \"GST pull-down assays and analysis of mutant RNase MRP RNA\",\n      \"pmids\": [\"15096576\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Precise RNA-binding determinants on RPP40 not defined at residue level\", \"No high-resolution structure of the assembled complex\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Distinguished RPP40's distribution across particle populations, showing it is present in essentially all RNase MRP particles in contrast to substoichiometric subunits.\",\n      \"evidence\": \"Glycerol gradient sedimentation and co-immunoprecipitation with VSV-tagged subunits\",\n      \"pmids\": [\"16723659\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of pan-particle association not tested\", \"Does not address pre-rRNA processing activity directly\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Probed a cellular-phenotype role for RPP40, linking it to pre-rRNA transcription and ribosomal protein gene expression that drive cancer-cell proliferation and invasion.\",\n      \"evidence\": \"Loss- and gain-of-function proliferation/migration/invasion assays and transcriptional analysis in HCC cell lines\",\n      \"pmids\": [\"40517827\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single lab, no mechanistic reconstitution or structural validation\", \"Direct molecular link between RNase P/MRP function and rRNA transcription program not established\", \"Causality versus correlation in transcriptional changes unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPP40's specific subunit contacts contribute to RNase P/MRP catalysis and substrate selection, and the molecular basis of its reported influence on rRNA transcription, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure assigning RPP40 a defined catalytic or substrate-positioning role\", \"Mechanism connecting RNase MRP subunit identity to pre-rRNA transcriptional output not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"complexes\": [\"RNase P\", \"RNase MRP\"],\n    \"partners\": [\"POP1\", \"RPP21\", \"RPP29\", \"RPP30\", \"RPP38\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}