{"gene":"RPP40","run_date":"2026-04-28T20:42:06","timeline":{"discoveries":[{"year":1998,"finding":"RPP40 (Rpp40) was identified as a protein subunit that co-purifies with catalytically active human RNase P holoenzyme; polyclonal antibodies against recombinant Rpp40 precipitate active holoenzyme, establishing it as a bona fide component of the RNase P ribonucleoprotein complex.","method":"Co-purification, immunoprecipitation of active holoenzyme with polyclonal antibodies against recombinant Rpp40","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 — reciprocal immunoprecipitation of active holoenzyme, replicated across multiple labs","pmids":["9630247"],"is_preprint":false},{"year":1999,"finding":"Rpp40 is one of at least eight protein subunits of the human RNase P tRNA processing enzyme in HeLa cells, as confirmed by immunoprecipitation of catalytically active RNase P.","method":"Immunoprecipitation of catalytically active RNase P from HeLa cells using antibodies against recombinant protein subunits","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 — immunoprecipitation of active enzyme, independently replicated","pmids":["10024167"],"is_preprint":false},{"year":2001,"finding":"Rpp40 participates in extensive protein-protein interactions with other subunits of human nuclear RNase P (including hPop1, Rpp21, Rpp29, Rpp30, and Rpp38), contributing to holoenzyme assembly.","method":"Yeast two-hybrid system with HeLa cell cDNA library","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 — yeast two-hybrid, interactions described as weak, single lab","pmids":["11158571"],"is_preprint":false},{"year":2004,"finding":"Rpp40 forms direct protein-protein interactions with multiple RNase MRP subunits and directly contacts the RNase MRP RNA, as part of a network of 19 direct protein-protein and 6 direct protein-RNA interactions that define the architecture of the human RNase MRP complex.","method":"GST pull-down experiments for protein-protein and protein-RNA interactions; analysis of mutant RNase MRP RNAs","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 — GST pull-down with RNA mutagenesis, multiple orthogonal interactions mapped, single lab","pmids":["15096576"],"is_preprint":false},{"year":2006,"finding":"Rpp40 is associated with both RNase MRP and RNase P complexes, and co-sediments with both 12S and 60–80S fractions, indicating it is a shared subunit likely present in all RNase MRP particles, in contrast to subunits that are RNase P-specific.","method":"Glycerol gradient sedimentation and coimmunoprecipitation with VSV-epitope-tagged subunits","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 — coimmunoprecipitation combined with sedimentation, multiple subunits compared, single lab","pmids":["16723659"],"is_preprint":false},{"year":2025,"finding":"RPP40 promotes HCC cell proliferation, migration, and invasion by coordinating transcription of pre-rRNA and expression of ribosomal protein genes, linking its RNase P/MRP function to ribosome biogenesis control in cancer cells.","method":"Loss-of-function and overexpression in HCC cell lines with phenotypic readouts (proliferation, migration, invasion assays) and transcriptional analysis of rRNA and ribosomal protein genes","journal":"Gene","confidence":"Low","confidence_rationale":"Tier 3 — single lab, cellular phenotype with partial pathway placement but limited mechanistic detail","pmids":["40517827"],"is_preprint":false}],"current_model":"RPP40 is a protein subunit shared between the human RNase P and RNase MRP ribonucleoprotein complexes, participating in both pre-tRNA processing and pre-rRNA processing; it is held in these complexes through direct protein-protein interactions with multiple other subunits and direct contacts with the complex RNA, and in cancer cells it additionally coordinates pre-rRNA transcription and ribosomal protein gene expression to promote cell proliferation and invasion."},"narrative":{"teleology":[{"year":1998,"claim":"Establishing RPP40 as a genuine RNase P subunit resolved the identity of proteins required for human nuclear pre-tRNA processing beyond the catalytic RNA.","evidence":"Co-purification and immunoprecipitation of catalytically active RNase P holoenzyme using anti-Rpp40 antibodies from HeLa cell extracts","pmids":["9630247"],"confidence":"High","gaps":["Role of RPP40 in catalysis versus holoenzyme stability not distinguished","Stoichiometry of RPP40 within the holoenzyme unknown"]},{"year":1999,"claim":"Confirmation that RPP40 is one of at least eight protein subunits of RNase P solidified the multi-subunit composition of the human enzyme.","evidence":"Immunoprecipitation of catalytically active RNase P from HeLa cells with antibodies against individual recombinant subunits","pmids":["10024167"],"confidence":"High","gaps":["Whether RPP40 is essential for catalytic activity or dispensable for in vitro cleavage not tested","Structural arrangement of RPP40 relative to H1 RNA not resolved"]},{"year":2001,"claim":"Mapping RPP40's protein–protein interaction network within RNase P revealed how multiple direct contacts (with hPop1, Rpp21, Rpp29, Rpp30, Rpp38) contribute to holoenzyme assembly.","evidence":"Yeast two-hybrid screens using HeLa cDNA library","pmids":["11158571"],"confidence":"Medium","gaps":["Interactions described as weak in yeast two-hybrid; not all validated by orthogonal pulldown","Which interactions are essential for holoenzyme integrity versus redundant not determined"]},{"year":2004,"claim":"Demonstrating that RPP40 contacts both protein subunits and the RNA component of RNase MRP established it as a dual-complex subunit with direct RNA-binding capacity.","evidence":"GST pull-down experiments with mutant RNase MRP RNAs mapping protein–protein and protein–RNA contacts","pmids":["15096576"],"confidence":"Medium","gaps":["Specific RNA elements or nucleotides contacted by RPP40 not mapped at high resolution","Whether RPP40 RNA contacts are required for MRP catalytic function not tested"]},{"year":2006,"claim":"Sedimentation analysis showing RPP40 co-fractionates with both 12S and 60–80S particles distinguished it as a constitutive shared subunit of RNase P and RNase MRP, unlike complex-specific factors.","evidence":"Glycerol gradient sedimentation combined with coimmunoprecipitation of VSV-epitope-tagged subunits","pmids":["16723659"],"confidence":"Medium","gaps":["Nature of the 60–80S particles containing RPP40 not fully characterized","Whether RPP40 partitions between the two complexes dynamically or is simultaneously present in both not resolved"]},{"year":2025,"claim":"Loss-of-function studies in hepatocellular carcinoma cells linked RPP40 to coordination of pre-rRNA transcription and ribosomal protein gene expression, extending its role beyond RNA processing to ribosome biogenesis control in cancer.","evidence":"Knockdown and overexpression in HCC cell lines with proliferation, migration, and invasion assays plus transcriptional profiling","pmids":["40517827"],"confidence":"Low","gaps":["Single-lab study in one cancer type without in vivo validation","Mechanism by which RPP40 influences pre-rRNA transcription (direct versus indirect) not defined","Whether ribosome biogenesis phenotype reflects canonical RNase MRP/P function or a moonlighting activity is unclear"]},{"year":null,"claim":"How RPP40 contributes to catalytic activity of RNase P and RNase MRP — whether it is essential for substrate recognition, cleavage chemistry, or structural integrity — remains mechanistically undefined.","evidence":"","pmids":[],"confidence":"High","gaps":["No reconstitution experiment testing RPP40's necessity for in vitro catalysis","No high-resolution structure of human RNase P or MRP with RPP40 resolved","No in vivo depletion study examining pre-tRNA or pre-rRNA processing defects in human cells"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,4]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,3,4]}],"complexes":["RNase P","RNase MRP"],"partners":["POP1","RPP21","RPP29","RPP30","RPP38"],"other_free_text":[]},"mechanistic_narrative":"RPP40 is a protein subunit shared by the human RNase P and RNase MRP ribonucleoprotein complexes, functioning in pre-tRNA and pre-rRNA processing. It was identified as a bona fide RNase P component through co-purification and immunoprecipitation of catalytically active holoenzyme [PMID:9630247, PMID:10024167], and participates in extensive protein–protein interactions with subunits including hPop1, Rpp21, Rpp29, Rpp30, and Rpp38, as well as direct contacts with RNase MRP RNA, contributing to the architectural assembly of both complexes [PMID:11158571, PMID:15096576]. Glycerol gradient sedimentation confirms RPP40 co-sediments with both 12S and 60–80S RNase MRP/P particles, establishing it as a constitutive shared subunit rather than a complex-specific factor [PMID:16723659]."},"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":84,"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":40,"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5740,"output_tokens":1328,"usd":0.01857},"stage2":{"model":"claude-opus-4-6","input_tokens":4564,"output_tokens":1727,"usd":0.098992},"total_usd":0.117562,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"RPP40 (Rpp40) was identified as a protein subunit that co-purifies with catalytically active human RNase P holoenzyme; polyclonal antibodies against recombinant Rpp40 precipitate active holoenzyme, establishing it as a bona fide component of the RNase P ribonucleoprotein complex.\",\n      \"method\": \"Co-purification, immunoprecipitation of active holoenzyme with polyclonal antibodies against recombinant Rpp40\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal immunoprecipitation of active holoenzyme, replicated across multiple labs\",\n      \"pmids\": [\"9630247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Rpp40 is one of at least eight protein subunits of the human RNase P tRNA processing enzyme in HeLa cells, as confirmed by immunoprecipitation of catalytically active RNase P.\",\n      \"method\": \"Immunoprecipitation of catalytically active RNase P from HeLa cells using antibodies against recombinant protein subunits\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — immunoprecipitation of active enzyme, independently replicated\",\n      \"pmids\": [\"10024167\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Rpp40 participates in extensive protein-protein interactions with other subunits of human nuclear RNase P (including hPop1, Rpp21, Rpp29, Rpp30, and Rpp38), contributing to holoenzyme assembly.\",\n      \"method\": \"Yeast two-hybrid system with HeLa cell cDNA library\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — yeast two-hybrid, interactions described as weak, single lab\",\n      \"pmids\": [\"11158571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Rpp40 forms direct protein-protein interactions with multiple RNase MRP subunits and directly contacts the RNase MRP RNA, as part of a network of 19 direct protein-protein and 6 direct protein-RNA interactions that define the architecture of the human RNase MRP complex.\",\n      \"method\": \"GST pull-down experiments for protein-protein and protein-RNA interactions; analysis of mutant RNase MRP RNAs\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — GST pull-down with RNA mutagenesis, multiple orthogonal interactions mapped, single lab\",\n      \"pmids\": [\"15096576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Rpp40 is associated with both RNase MRP and RNase P complexes, and co-sediments with both 12S and 60–80S fractions, indicating it is a shared subunit likely present in all RNase MRP particles, in contrast to subunits that are RNase P-specific.\",\n      \"method\": \"Glycerol gradient sedimentation and coimmunoprecipitation with VSV-epitope-tagged subunits\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — coimmunoprecipitation combined with sedimentation, multiple subunits compared, single lab\",\n      \"pmids\": [\"16723659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RPP40 promotes HCC cell proliferation, migration, and invasion by coordinating transcription of pre-rRNA and expression of ribosomal protein genes, linking its RNase P/MRP function to ribosome biogenesis control in cancer cells.\",\n      \"method\": \"Loss-of-function and overexpression in HCC cell lines with phenotypic readouts (proliferation, migration, invasion assays) and transcriptional analysis of rRNA and ribosomal protein genes\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, cellular phenotype with partial pathway placement but limited mechanistic detail\",\n      \"pmids\": [\"40517827\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPP40 is a protein subunit shared between the human RNase P and RNase MRP ribonucleoprotein complexes, participating in both pre-tRNA processing and pre-rRNA processing; it is held in these complexes through direct protein-protein interactions with multiple other subunits and direct contacts with the complex RNA, and in cancer cells it additionally coordinates pre-rRNA transcription and ribosomal protein gene expression to promote cell proliferation and invasion.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RPP40 is a protein subunit shared by the human RNase P and RNase MRP ribonucleoprotein complexes, functioning in pre-tRNA and pre-rRNA processing. It was identified as a bona fide RNase P component through co-purification and immunoprecipitation of catalytically active holoenzyme [PMID:9630247, PMID:10024167], and participates in extensive protein–protein interactions with subunits including hPop1, Rpp21, Rpp29, Rpp30, and Rpp38, as well as direct contacts with RNase MRP RNA, contributing to the architectural assembly of both complexes [PMID:11158571, PMID:15096576]. Glycerol gradient sedimentation confirms RPP40 co-sediments with both 12S and 60–80S RNase MRP/P particles, establishing it as a constitutive shared subunit rather than a complex-specific factor [PMID:16723659].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Establishing RPP40 as a genuine RNase P subunit resolved the identity of proteins required for human nuclear pre-tRNA processing beyond the catalytic RNA.\",\n      \"evidence\": \"Co-purification and immunoprecipitation of catalytically active RNase P holoenzyme using anti-Rpp40 antibodies from HeLa cell extracts\",\n      \"pmids\": [\"9630247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Role of RPP40 in catalysis versus holoenzyme stability not distinguished\",\n        \"Stoichiometry of RPP40 within the holoenzyme unknown\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Confirmation that RPP40 is one of at least eight protein subunits of RNase P solidified the multi-subunit composition of the human enzyme.\",\n      \"evidence\": \"Immunoprecipitation of catalytically active RNase P from HeLa cells with antibodies against individual recombinant subunits\",\n      \"pmids\": [\"10024167\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether RPP40 is essential for catalytic activity or dispensable for in vitro cleavage not tested\",\n        \"Structural arrangement of RPP40 relative to H1 RNA not resolved\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Mapping RPP40's protein–protein interaction network within RNase P revealed how multiple direct contacts (with hPop1, Rpp21, Rpp29, Rpp30, Rpp38) contribute to holoenzyme assembly.\",\n      \"evidence\": \"Yeast two-hybrid screens using HeLa cDNA library\",\n      \"pmids\": [\"11158571\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interactions described as weak in yeast two-hybrid; not all validated by orthogonal pulldown\",\n        \"Which interactions are essential for holoenzyme integrity versus redundant not determined\"\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrating that RPP40 contacts both protein subunits and the RNA component of RNase MRP established it as a dual-complex subunit with direct RNA-binding capacity.\",\n      \"evidence\": \"GST pull-down experiments with mutant RNase MRP RNAs mapping protein–protein and protein–RNA contacts\",\n      \"pmids\": [\"15096576\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific RNA elements or nucleotides contacted by RPP40 not mapped at high resolution\",\n        \"Whether RPP40 RNA contacts are required for MRP catalytic function not tested\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Sedimentation analysis showing RPP40 co-fractionates with both 12S and 60–80S particles distinguished it as a constitutive shared subunit of RNase P and RNase MRP, unlike complex-specific factors.\",\n      \"evidence\": \"Glycerol gradient sedimentation combined with coimmunoprecipitation of VSV-epitope-tagged subunits\",\n      \"pmids\": [\"16723659\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Nature of the 60–80S particles containing RPP40 not fully characterized\",\n        \"Whether RPP40 partitions between the two complexes dynamically or is simultaneously present in both not resolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Loss-of-function studies in hepatocellular carcinoma cells linked RPP40 to coordination of pre-rRNA transcription and ribosomal protein gene expression, extending its role beyond RNA processing to ribosome biogenesis control in cancer.\",\n      \"evidence\": \"Knockdown and overexpression in HCC cell lines with proliferation, migration, and invasion assays plus transcriptional profiling\",\n      \"pmids\": [\"40517827\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single-lab study in one cancer type without in vivo validation\",\n        \"Mechanism by which RPP40 influences pre-rRNA transcription (direct versus indirect) not defined\",\n        \"Whether ribosome biogenesis phenotype reflects canonical RNase MRP/P function or a moonlighting activity is unclear\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPP40 contributes to catalytic activity of RNase P and RNase MRP — whether it is essential for substrate recognition, cleavage chemistry, or structural integrity — remains mechanistically undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No reconstitution experiment testing RPP40's necessity for in vitro catalysis\",\n        \"No high-resolution structure of human RNase P or MRP with RPP40 resolved\",\n        \"No in vivo depletion study examining pre-tRNA or pre-rRNA processing defects in human cells\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 3, 4]}\n    ],\n    \"complexes\": [\n      \"RNase P\",\n      \"RNase MRP\"\n    ],\n    \"partners\": [\n      \"POP1\",\n      \"RPP21\",\n      \"RPP29\",\n      \"RPP30\",\n      \"RPP38\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}