{"gene":"RPP38","run_date":"2026-06-10T07:46:27","timeline":{"discoveries":[{"year":1997,"finding":"RPP38 (p38) was identified as a protein subunit of human RNase P that copurifies with the enzyme activity from HeLa cells; it is one of six polypeptides (14, 20, 25, 30, 38, 40 kDa) that copurify with RNase P, and scleroderma autoimmune sera that immunodeplete RNase P activity react specifically with p38 on immunoblots.","method":"2000-fold purification of human RNase P from HeLa cells, immunodepletion with scleroderma sera, immunoblotting, peptide sequencing, cDNA cloning","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — biochemical purification with functional immunodepletion assay, peptide sequencing, and molecular cloning; foundational characterization paper","pmids":["9037013"],"is_preprint":false},{"year":1998,"finding":"Polyclonal antibodies raised against recombinant Rpp38 recognize the corresponding protein associated with purified RNase P and precipitate catalytically active holoenzyme, confirming Rpp38 is a genuine subunit of the active RNase P complex.","method":"Recombinant protein production, polyclonal antibody generation, immunoprecipitation of active holoenzyme, immunoblotting","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal immunoprecipitation of active enzyme, multiple orthogonal validations across labs","pmids":["9630247"],"is_preprint":false},{"year":1999,"finding":"Rpp38 is localized to the nucleolus, where it is uniformly distributed (unlike Rpp14 and Rpp29 which are confined to the dense fibrillar component). Rpp38 possesses a functional domain required for subnucleolar localization and can localize a reporter protein to nucleoli.","method":"Immunofluorescence microscopy, reporter protein localization assay in cultured cells, biochemical fractionation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization by imaging with functional reporter assay, domain dissection, single lab with multiple orthogonal methods","pmids":["10444065"],"is_preprint":false},{"year":1999,"finding":"Rpp38 is associated with the RNase MRP complex as well as RNase P. VSV-tagged Rpp38 expressed in HeLa cells co-immunoprecipitates both RNase P and RNase MRP complexes. UV crosslinking followed by anti-Rpp38 immunoprecipitation identified Rpp38 as the ~40 kDa protein that associates with the central part of MRP RNA (nt 86-176).","method":"VSV-epitope tagging, immunoprecipitation in HeLa cells, UV crosslinking followed by immunoprecipitation with anti-Rpp38 antibodies","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus UV crosslinking in cells, two orthogonal methods, single lab","pmids":["10199568"],"is_preprint":false},{"year":2001,"finding":"Rpp38 participates in protein-protein interactions within the human nuclear RNase P holoenzyme complex, as detected by yeast two-hybrid analysis. These interactions are weak, consistent with a loosely assembled protein core.","method":"Yeast two-hybrid system using protein subunits of human nuclear RNase P","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid only, but interactions confirmed for multiple subunits with consistent results","pmids":["11158571"],"is_preprint":false},{"year":2001,"finding":"Rpp38 directly interacts with H1 RNA, the RNA subunit of human nuclear RNase P, as demonstrated by yeast three-hybrid assay and confirmed by UV crosslinking of the purified holoenzyme.","method":"Yeast three-hybrid system, UV crosslinking of purified RNase P holoenzyme","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — two orthogonal methods (three-hybrid in vivo and UV crosslinking of purified complex), results are mutually confirmatory","pmids":["11455963"],"is_preprint":false},{"year":2001,"finding":"A basic domain in Rpp38 is responsible for its nucleolar accumulation, and Rpp38 can accumulate in the nucleolus independently of its association with the RNase MRP and RNase P complexes. A deletion mutant of Rpp38 was identified that preferentially associates with the RNase MRP complex rather than RNase P, providing a clue about differences in protein composition between the two complexes.","method":"Transfection of GFP-tagged deletion mutants, fluorescence microscopy, co-immunoprecipitation","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct imaging with domain deletion mutants and co-immunoprecipitation, mechanistic dissection with functional readout","pmids":["11694598"],"is_preprint":false},{"year":2002,"finding":"The previously defined Th40 autoantigen is identical to Rpp38. Reconstitution and UV crosslinking experiments showed that Rpp38 does NOT directly bind to the P3 domain of RNase MRP RNA; the previously reported 40 kDa species associating with the P3 domain appeared to consist of Rpp20 and/or Rpp25.","method":"Reconstitution experiments, UV crosslinking, immunoprecipitation with patient antisera and recombinant proteins","journal":"Arthritis and rheumatism","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reconstitution and UV crosslinking with multiple controls; negative finding regarding P3 domain binding rigorously established","pmids":["12483731"],"is_preprint":false},{"year":2003,"finding":"Constitutive overexpression of exogenous tagged Rpp38 in HeLa cells impairs processing of tRNA precursors and affects cleavage and steady-state levels of the 3' ITS1 of rRNA. RNase P purified from these cells shows reduced activity in vitro. Inhibition of Rpp38 by siRNA causes accumulation of the initiator methionine tRNA precursor. Knockdown of Rpp38 coordinately inhibits expression of other RNase P protein subunits (but not H1 RNA).","method":"Stable transfection in HeLa cells, Northern blotting for tRNA precursors, in vitro RNase P activity assay, siRNA knockdown","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — loss-of-function (siRNA) and gain-of-function with defined molecular phenotype (tRNA processing defect), in vitro activity confirmation, single lab with multiple orthogonal approaches","pmids":["12907726"],"is_preprint":false},{"year":2003,"finding":"Targeted inhibition of Rpp38 expression using an external guide sequence (EGS) reduces both Rpp38 mRNA and protein levels within 24 hours. This also coordinately inhibits four other RNase P protein subunits and their mRNAs, without affecting the remaining subunits or H1 RNA, suggesting co-regulated expression of a subset of RNase P protein genes.","method":"EGS technology (external guide sequence targeting Rpp38 mRNA), transient transfection, RT-PCR, immunoblotting","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — specific knockdown confirmed at both mRNA and protein levels, coordinate inhibition replicated in subsequent studies","pmids":["12552092"],"is_preprint":false},{"year":2004,"finding":"In the human RNase MRP complex, Rpp38 directly interacts with multiple protein subunits (total of 19 direct protein-protein interactions were mapped among all subunits) and directly binds to RNase MRP RNA, contributing to a model of ribonucleoprotein particle architecture.","method":"GST pull-down experiments with recombinant proteins and MRP RNA fragments including deletion mutants","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — GST pull-down for protein-protein and protein-RNA interactions, systematic mapping, single lab","pmids":["15096576"],"is_preprint":false},{"year":2005,"finding":"A regulatable EGS targeting Rpp38 stably integrated into a human cell line effectively reduces Rpp38 protein levels upon induction, and also inhibits several other (but not all) RNase P protein subunits at both mRNA and protein levels.","method":"Stably integrated inducible pol III promoter system, EGS targeting Rpp38, immunoblotting, RT-PCR","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — regulated knockdown system confirming coordinate inhibition, extends prior EGS work","pmids":["16131590"],"is_preprint":false},{"year":2006,"finding":"Rpp38 (along with hPop1, Rpp40, and Rpp30) is associated with both the 12S and the 60-80S RNase MRP complexes, whereas some other subunits are restricted to 12S. Co-immunoprecipitation with VSV-tagged subunits confirmed that Rpp38 is associated with RNase MRP complexes.","method":"Glycerol gradient sedimentation, co-immunoprecipitation with VSV-epitope-tagged protein subunits","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — two orthogonal biochemical methods (sedimentation + co-IP), single lab","pmids":["16723659"],"is_preprint":false},{"year":2006,"finding":"Computational analysis suggests that the yeast RNase P/MRP protein Pop3p has the same L7Ae/L30e RNA-binding fold as human Rpp38, and that a K-turn motif in RNase P/MRP RNAs may serve as a binding site for Pop3p/Rpp38 proteins.","method":"Profile-based computational searches, phylogenetic analysis, structural prediction","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation of K-turn binding in this paper","pmids":["16998185"],"is_preprint":false},{"year":2016,"finding":"Crystal structure of the archaeal Rpp38 homologue PhoRpp38 (from Pyrococcus horikoshii) in complex with a K-turn-containing RNA stem-loop (SL12M) was determined at 3.4 Å resolution. Key residues Lys35, Asn38, Glu39, Lys42 interact with G·A and A·G pairs in the K-turn, while Ile93, Glu94, Val95 contact the 3-nucleotide bulge. Structure-based mutagenesis confirmed that the same residues mediate binding to both SL12 and SL16 K-turns in PhoRpp38 RNA.","method":"X-ray crystallography (3.4 Å), structure-based mutagenesis, pull-down assay","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with mutagenesis validation, single lab but multiple orthogonal methods","pmids":["27114305"],"is_preprint":false},{"year":2017,"finding":"Rpp38 was explicitly tested and found NOT to be recruited to laser-microirradiated DNA damage sites, in contrast to Rpp29 and Rpp21 which are recruited and play a role in homology-directed repair of double-strand breaks.","method":"Live-cell laser microirradiation, fluorescence microscopy (negative result for Rpp38 recruitment)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct live imaging experiment with negative result for Rpp38; negative finding is experimentally established","pmids":["28432356"],"is_preprint":false},{"year":2018,"finding":"Improved crystal structures of archaeal Rpp38 homologue PhoRpp38 in complex with K-turn motifs were determined at 2.1 Å (P12.2) and 3.1 Å (P12.1) resolution. Additional contact residues (Thr37, Asp59, Lys84, Ala96, Ala98) interacting with the three-nucleotide bulge were identified. PhoRpp38 with PhoRpp21 and PhoRpp29 was co-purified with an extended stem-loop containing P10-P12.2.","method":"X-ray crystallography (2.1 Å and 3.1 Å), affinity purification of multi-protein RNA complex","journal":"Acta crystallographica. Section F, Structural biology communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — high-resolution crystal structures with detailed contact identification, extends and confirms prior structural work","pmids":["29372908"],"is_preprint":false}],"current_model":"RPP38 is a protein subunit of both human RNase P and RNase MRP ribonucleoprotein complexes that directly binds H1 RNA via an L7Ae/L30e-family domain recognizing K-turn motifs (established by structural studies of its archaeal homologue), localizes to the nucleolus via an intrinsic basic domain independently of complex association, participates in multiple protein-protein interactions within the holoenzyme, and is required for normal tRNA precursor processing — with its knockdown causing tRNA precursor accumulation and coordinate reduction of other RNase P protein subunits."},"narrative":{"mechanistic_narrative":"RPP38 (p38/Th40) is a shared protein subunit of the human RNase P and RNase MRP ribonucleoprotein endonucleases, required for normal processing of tRNA precursors [PMID:9037013, PMID:10199568, PMID:12907726]. It was first isolated as one of several polypeptides copurifying with catalytically active RNase P and is a target of scleroderma autoimmune sera; antibodies against it immunoprecipitate active holoenzyme, establishing it as a genuine subunit [PMID:9037013, PMID:9630247]. RPP38 directly binds the RNA subunit of RNase P (H1 RNA) and also associates with RNase MRP RNA, integrating into both complexes through multiple weak protein-protein contacts within a loosely assembled protein core [PMID:10199568, PMID:11455963, PMID:15096576, PMID:11158571]. Structural studies of its archaeal homologue show that RPP38 belongs to the L7Ae/L30e fold family and recognizes K-turn motifs in the RNase P/MRP RNA via a defined set of contact residues [PMID:27114305, PMID:29372908]. It localizes uniformly throughout the nucleolus, directed by an intrinsic basic domain that targets it to nucleoli independently of complex assembly [PMID:10444065, PMID:11694598]. Functionally, knockdown of RPP38 causes accumulation of tRNA precursors, reduces RNase P activity in vitro, and coordinately lowers the levels of a subset of other RNase P protein subunits without affecting H1 RNA, indicating co-regulated expression of these subunits [PMID:12907726, PMID:12552092]. Unlike the RNase P subunits Rpp29 and Rpp21, RPP38 is not recruited to sites of DNA damage [PMID:28432356].","teleology":[{"year":1997,"claim":"Established that a 38 kDa polypeptide is a bona fide component of human RNase P, defining the protein composition of a previously RNA-centric enzyme.","evidence":"2000-fold biochemical purification of RNase P from HeLa cells with scleroderma serum immunodepletion, peptide sequencing, and cDNA cloning","pmids":["9037013"],"confidence":"High","gaps":["Copurification alone did not prove direct association with the active enzyme","No RNA- or protein-binding partners identified"]},{"year":1998,"claim":"Confirmed Rpp38 is an integral subunit of the catalytically active holoenzyme rather than a copurifying contaminant.","evidence":"Recombinant-protein-derived polyclonal antibodies immunoprecipitating active RNase P holoenzyme","pmids":["9630247"],"confidence":"High","gaps":["Did not define which RNA or proteins Rpp38 contacts within the complex"]},{"year":1999,"claim":"Showed Rpp38 is shared between RNase P and RNase MRP and defined its nucleolar localization, linking it to two distinct processing enzymes.","evidence":"VSV-tagged co-immunoprecipitation of both complexes, UV crosslinking to MRP RNA nt 86-176, and immunofluorescence with a nucleolar-targeting reporter assay","pmids":["10199568","10444065"],"confidence":"High","gaps":["Did not identify the molecular determinant of complex selectivity","Distinct from Rpp14/Rpp29 dense-fibrillar-component localization, but functional meaning unresolved"]},{"year":2001,"claim":"Mapped Rpp38's molecular contacts—direct binding to H1 RNA and weak protein-protein interactions—and localized its nucleolar-targeting basic domain, building the architecture of the particle.","evidence":"Yeast three-hybrid and UV crosslinking for H1 RNA binding; yeast two-hybrid for inter-subunit contacts; GFP deletion mutants and co-IP for the basic nucleolar domain","pmids":["11455963","11158571","11694598"],"confidence":"High","gaps":["Two-hybrid interactions were weak and not all reciprocally validated","Nucleolar targeting independent of complex association left functional rationale open"]},{"year":2002,"claim":"Resolved the identity of the Th40 autoantigen as Rpp38 and corrected the prior assignment that Rpp38 binds the MRP P3 domain.","evidence":"Reconstitution and UV crosslinking with recombinant proteins and patient antisera","pmids":["12483731"],"confidence":"High","gaps":["The precise MRP RNA element bound by Rpp38 within the complex remained to be pinned down"]},{"year":2003,"claim":"Demonstrated a functional requirement for Rpp38 in tRNA precursor processing and uncovered coordinate co-regulation of a subset of RNase P protein subunits.","evidence":"Stable overexpression, siRNA and EGS knockdown in HeLa cells with Northern blotting, in vitro RNase P activity assays, and RT-PCR/immunoblotting of other subunits","pmids":["12907726","12552092"],"confidence":"Medium","gaps":["Mechanism of coordinate subunit co-regulation not defined","Whether processing defects are direct or secondary to subunit depletion unresolved"]},{"year":2004,"claim":"Placed Rpp38 within an interaction map of the RNase MRP RNP, showing it directly binds both MRP RNA and multiple protein subunits.","evidence":"GST pull-down assays with recombinant subunits and MRP RNA fragment/deletion mutants","pmids":["15096576"],"confidence":"Medium","gaps":["Pull-down interactions not confirmed in the assembled holoenzyme","Stoichiometry and spatial arrangement not determined"]},{"year":2006,"claim":"Refined the picture of Rpp38 distribution across MRP complex states and the co-regulated subunit set.","evidence":"Glycerol gradient sedimentation and VSV-tagged co-IP across 12S and 60-80S MRP complexes; inducible EGS knockdown system","pmids":["16723659","16131590"],"confidence":"Medium","gaps":["Functional difference between 12S and larger MRP complexes for Rpp38 unclear"]},{"year":2016,"claim":"Provided atomic-level mechanism for how Rpp38 recognizes its RNA target by solving the archaeal homologue bound to a K-turn motif.","evidence":"X-ray crystallography of PhoRpp38–SL12M (3.4 Å) with structure-based mutagenesis and pull-down validation","pmids":["27114305"],"confidence":"High","gaps":["Structure is of the archaeal homologue, not human RPP38","K-turn binding by human RPP38 within its complexes not directly co-crystallized"]},{"year":2017,"claim":"Distinguished Rpp38 from other RNase P subunits in moonlighting function by showing it is not recruited to DNA damage sites.","evidence":"Live-cell laser microirradiation imaging (negative result for Rpp38)","pmids":["28432356"],"confidence":"Medium","gaps":["Does not exclude DNA-damage roles under other conditions","Negative result for a single recruitment readout"]},{"year":2018,"claim":"Extended the structural basis of K-turn recognition and demonstrated Rpp38 assembly with neighboring subunits on an extended RNA stem-loop.","evidence":"Higher-resolution X-ray structures of PhoRpp38–K-turn complexes (2.1 Å, 3.1 Å) and co-purification of PhoRpp38/Rpp21/Rpp29 with P10-P12.2 RNA","pmids":["29372908"],"confidence":"High","gaps":["Archaeal system; human subassembly architecture not directly resolved","Catalytic contribution of Rpp38 to substrate cleavage not addressed"]},{"year":null,"claim":"How RPP38-mediated K-turn recognition is integrated into substrate selection and catalysis by the human RNase P and MRP holoenzymes, and the mechanism of coordinate co-regulation of RNase P subunits, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No human RPP38–RNA structure within the assembled holoenzyme","Mechanism linking RPP38 depletion to loss of other subunits unknown","Functional partition of RPP38 between RNase P and MRP roles undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[3,5,10,14,16]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[2,6]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,3,8]}],"complexes":["RNase P","RNase MRP"],"partners":["POP1","RPP40","RPP30","RPP29","RPP21","RPP20","RPP25"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P78345","full_name":"Ribonuclease P protein subunit p38","aliases":[],"length_aa":283,"mass_kda":31.8,"function":"Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:10444065, PubMed:30454648, PubMed:9037013, 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/P78345/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPP38","classification":"Common Essential","n_dependent_lines":905,"n_total_lines":1208,"dependency_fraction":0.7491721854304636},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SSB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RPP38","total_profiled":1310},"omim":[{"mim_id":"608513","title":"RIBONUCLEASE P, RNA COMPONENT H1; RPPH1","url":"https://www.omim.org/entry/608513"},{"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"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoli","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPP38"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"P78345","domains":[{"cath_id":"3.30.1330.30","chopping":"58-63_103-199","consensus_level":"medium","plddt":94.5861,"start":58,"end":199}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P78345","model_url":"https://alphafold.ebi.ac.uk/files/AF-P78345-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P78345-F1-predicted_aligned_error_v6.png","plddt_mean":72.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPP38","jax_strain_url":"https://www.jax.org/strain/search?query=RPP38"},"sequence":{"accession":"P78345","fasta_url":"https://rest.uniprot.org/uniprotkb/P78345.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P78345/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P78345"}},"corpus_meta":[{"pmid":"9037013","id":"PMC_9037013","title":"Characterization of two scleroderma 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Section F, Structural biology communications","url":"https://pubmed.ncbi.nlm.nih.gov/29372908","citation_count":8,"is_preprint":false},{"pmid":"31323671","id":"PMC_31323671","title":"Autoantibodies to a novel Rpp38 (Th/To) derived B-cell epitope are specific for systemic sclerosis and associate with a distinct clinical phenotype.","date":"2019","source":"Rheumatology (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/31323671","citation_count":7,"is_preprint":false},{"pmid":"12907726","id":"PMC_12907726","title":"Alterations in the intracellular level of a protein subunit of human RNase P affect processing of tRNA precursors.","date":"2003","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/12907726","citation_count":7,"is_preprint":false},{"pmid":"22162665","id":"PMC_22162665","title":"Assembly of the complex between archaeal RNase P proteins RPP30 and Pop5.","date":"2011","source":"Archaea (Vancouver, B.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/22162665","citation_count":7,"is_preprint":false},{"pmid":"16131590","id":"PMC_16131590","title":"Regulated expression of functional external guide sequences in mammalian cells using a U6 RNA polymerase III promoter.","date":"2005","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/16131590","citation_count":4,"is_preprint":false},{"pmid":"38116482","id":"PMC_38116482","title":"Genetic Switches between Cancer and Emphysema Resolution of Cigarette-Smoke Induced Inflammation.","date":"2019","source":"EC pulmonology and respiratory medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38116482","citation_count":1,"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":16422,"output_tokens":4090,"usd":0.055308,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11877,"output_tokens":3411,"usd":0.07233,"stage2_stop_reason":"end_turn"},"total_usd":0.127638,"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\": 1997,\n      \"finding\": \"RPP38 (p38) was identified as a protein subunit of human RNase P that copurifies with the enzyme activity from HeLa cells; it is one of six polypeptides (14, 20, 25, 30, 38, 40 kDa) that copurify with RNase P, and scleroderma autoimmune sera that immunodeplete RNase P activity react specifically with p38 on immunoblots.\",\n      \"method\": \"2000-fold purification of human RNase P from HeLa cells, immunodepletion with scleroderma sera, immunoblotting, peptide sequencing, cDNA cloning\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — biochemical purification with functional immunodepletion assay, peptide sequencing, and molecular cloning; foundational characterization paper\",\n      \"pmids\": [\"9037013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Polyclonal antibodies raised against recombinant Rpp38 recognize the corresponding protein associated with purified RNase P and precipitate catalytically active holoenzyme, confirming Rpp38 is a genuine subunit of the active RNase P complex.\",\n      \"method\": \"Recombinant protein production, polyclonal antibody generation, immunoprecipitation of active holoenzyme, immunoblotting\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal immunoprecipitation of active enzyme, multiple orthogonal validations across labs\",\n      \"pmids\": [\"9630247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Rpp38 is localized to the nucleolus, where it is uniformly distributed (unlike Rpp14 and Rpp29 which are confined to the dense fibrillar component). Rpp38 possesses a functional domain required for subnucleolar localization and can localize a reporter protein to nucleoli.\",\n      \"method\": \"Immunofluorescence microscopy, reporter protein localization assay in cultured cells, biochemical fractionation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by imaging with functional reporter assay, domain dissection, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"10444065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Rpp38 is associated with the RNase MRP complex as well as RNase P. VSV-tagged Rpp38 expressed in HeLa cells co-immunoprecipitates both RNase P and RNase MRP complexes. UV crosslinking followed by anti-Rpp38 immunoprecipitation identified Rpp38 as the ~40 kDa protein that associates with the central part of MRP RNA (nt 86-176).\",\n      \"method\": \"VSV-epitope tagging, immunoprecipitation in HeLa cells, UV crosslinking followed by immunoprecipitation with anti-Rpp38 antibodies\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus UV crosslinking in cells, two orthogonal methods, single lab\",\n      \"pmids\": [\"10199568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Rpp38 participates in protein-protein interactions within the human nuclear RNase P holoenzyme complex, as detected by yeast two-hybrid analysis. These interactions are weak, consistent with a loosely assembled protein core.\",\n      \"method\": \"Yeast two-hybrid system using protein subunits of human nuclear RNase P\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid only, but interactions confirmed for multiple subunits with consistent results\",\n      \"pmids\": [\"11158571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Rpp38 directly interacts with H1 RNA, the RNA subunit of human nuclear RNase P, as demonstrated by yeast three-hybrid assay and confirmed by UV crosslinking of the purified holoenzyme.\",\n      \"method\": \"Yeast three-hybrid system, UV crosslinking of purified RNase P holoenzyme\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two orthogonal methods (three-hybrid in vivo and UV crosslinking of purified complex), results are mutually confirmatory\",\n      \"pmids\": [\"11455963\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"A basic domain in Rpp38 is responsible for its nucleolar accumulation, and Rpp38 can accumulate in the nucleolus independently of its association with the RNase MRP and RNase P complexes. A deletion mutant of Rpp38 was identified that preferentially associates with the RNase MRP complex rather than RNase P, providing a clue about differences in protein composition between the two complexes.\",\n      \"method\": \"Transfection of GFP-tagged deletion mutants, fluorescence microscopy, co-immunoprecipitation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging with domain deletion mutants and co-immunoprecipitation, mechanistic dissection with functional readout\",\n      \"pmids\": [\"11694598\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The previously defined Th40 autoantigen is identical to Rpp38. Reconstitution and UV crosslinking experiments showed that Rpp38 does NOT directly bind to the P3 domain of RNase MRP RNA; the previously reported 40 kDa species associating with the P3 domain appeared to consist of Rpp20 and/or Rpp25.\",\n      \"method\": \"Reconstitution experiments, UV crosslinking, immunoprecipitation with patient antisera and recombinant proteins\",\n      \"journal\": \"Arthritis and rheumatism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reconstitution and UV crosslinking with multiple controls; negative finding regarding P3 domain binding rigorously established\",\n      \"pmids\": [\"12483731\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Constitutive overexpression of exogenous tagged Rpp38 in HeLa cells impairs processing of tRNA precursors and affects cleavage and steady-state levels of the 3' ITS1 of rRNA. RNase P purified from these cells shows reduced activity in vitro. Inhibition of Rpp38 by siRNA causes accumulation of the initiator methionine tRNA precursor. Knockdown of Rpp38 coordinately inhibits expression of other RNase P protein subunits (but not H1 RNA).\",\n      \"method\": \"Stable transfection in HeLa cells, Northern blotting for tRNA precursors, in vitro RNase P activity assay, siRNA knockdown\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function (siRNA) and gain-of-function with defined molecular phenotype (tRNA processing defect), in vitro activity confirmation, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"12907726\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Targeted inhibition of Rpp38 expression using an external guide sequence (EGS) reduces both Rpp38 mRNA and protein levels within 24 hours. This also coordinately inhibits four other RNase P protein subunits and their mRNAs, without affecting the remaining subunits or H1 RNA, suggesting co-regulated expression of a subset of RNase P protein genes.\",\n      \"method\": \"EGS technology (external guide sequence targeting Rpp38 mRNA), transient transfection, RT-PCR, immunoblotting\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — specific knockdown confirmed at both mRNA and protein levels, coordinate inhibition replicated in subsequent studies\",\n      \"pmids\": [\"12552092\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"In the human RNase MRP complex, Rpp38 directly interacts with multiple protein subunits (total of 19 direct protein-protein interactions were mapped among all subunits) and directly binds to RNase MRP RNA, contributing to a model of ribonucleoprotein particle architecture.\",\n      \"method\": \"GST pull-down experiments with recombinant proteins and MRP RNA fragments including deletion mutants\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — GST pull-down for protein-protein and protein-RNA interactions, systematic mapping, single lab\",\n      \"pmids\": [\"15096576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"A regulatable EGS targeting Rpp38 stably integrated into a human cell line effectively reduces Rpp38 protein levels upon induction, and also inhibits several other (but not all) RNase P protein subunits at both mRNA and protein levels.\",\n      \"method\": \"Stably integrated inducible pol III promoter system, EGS targeting Rpp38, immunoblotting, RT-PCR\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — regulated knockdown system confirming coordinate inhibition, extends prior EGS work\",\n      \"pmids\": [\"16131590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Rpp38 (along with hPop1, Rpp40, and Rpp30) is associated with both the 12S and the 60-80S RNase MRP complexes, whereas some other subunits are restricted to 12S. Co-immunoprecipitation with VSV-tagged subunits confirmed that Rpp38 is associated with RNase MRP complexes.\",\n      \"method\": \"Glycerol gradient sedimentation, co-immunoprecipitation with VSV-epitope-tagged protein subunits\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — two orthogonal biochemical methods (sedimentation + co-IP), single lab\",\n      \"pmids\": [\"16723659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Computational analysis suggests that the yeast RNase P/MRP protein Pop3p has the same L7Ae/L30e RNA-binding fold as human Rpp38, and that a K-turn motif in RNase P/MRP RNAs may serve as a binding site for Pop3p/Rpp38 proteins.\",\n      \"method\": \"Profile-based computational searches, phylogenetic analysis, structural prediction\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation of K-turn binding in this paper\",\n      \"pmids\": [\"16998185\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of the archaeal Rpp38 homologue PhoRpp38 (from Pyrococcus horikoshii) in complex with a K-turn-containing RNA stem-loop (SL12M) was determined at 3.4 Å resolution. Key residues Lys35, Asn38, Glu39, Lys42 interact with G·A and A·G pairs in the K-turn, while Ile93, Glu94, Val95 contact the 3-nucleotide bulge. Structure-based mutagenesis confirmed that the same residues mediate binding to both SL12 and SL16 K-turns in PhoRpp38 RNA.\",\n      \"method\": \"X-ray crystallography (3.4 Å), structure-based mutagenesis, pull-down assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with mutagenesis validation, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"27114305\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Rpp38 was explicitly tested and found NOT to be recruited to laser-microirradiated DNA damage sites, in contrast to Rpp29 and Rpp21 which are recruited and play a role in homology-directed repair of double-strand breaks.\",\n      \"method\": \"Live-cell laser microirradiation, fluorescence microscopy (negative result for Rpp38 recruitment)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live imaging experiment with negative result for Rpp38; negative finding is experimentally established\",\n      \"pmids\": [\"28432356\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Improved crystal structures of archaeal Rpp38 homologue PhoRpp38 in complex with K-turn motifs were determined at 2.1 Å (P12.2) and 3.1 Å (P12.1) resolution. Additional contact residues (Thr37, Asp59, Lys84, Ala96, Ala98) interacting with the three-nucleotide bulge were identified. PhoRpp38 with PhoRpp21 and PhoRpp29 was co-purified with an extended stem-loop containing P10-P12.2.\",\n      \"method\": \"X-ray crystallography (2.1 Å and 3.1 Å), affinity purification of multi-protein RNA complex\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — high-resolution crystal structures with detailed contact identification, extends and confirms prior structural work\",\n      \"pmids\": [\"29372908\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPP38 is a protein subunit of both human RNase P and RNase MRP ribonucleoprotein complexes that directly binds H1 RNA via an L7Ae/L30e-family domain recognizing K-turn motifs (established by structural studies of its archaeal homologue), localizes to the nucleolus via an intrinsic basic domain independently of complex association, participates in multiple protein-protein interactions within the holoenzyme, and is required for normal tRNA precursor processing — with its knockdown causing tRNA precursor accumulation and coordinate reduction of other RNase P protein subunits.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPP38 (p38/Th40) is a shared protein subunit of the human RNase P and RNase MRP ribonucleoprotein endonucleases, required for normal processing of tRNA precursors [#0, #3, #8]. It was first isolated as one of several polypeptides copurifying with catalytically active RNase P and is a target of scleroderma autoimmune sera; antibodies against it immunoprecipitate active holoenzyme, establishing it as a genuine subunit [#0, #1]. RPP38 directly binds the RNA subunit of RNase P (H1 RNA) and also associates with RNase MRP RNA, integrating into both complexes through multiple weak protein-protein contacts within a loosely assembled protein core [#3, #5, #10, #4]. Structural studies of its archaeal homologue show that RPP38 belongs to the L7Ae/L30e fold family and recognizes K-turn motifs in the RNase P/MRP RNA via a defined set of contact residues [#14, #16]. It localizes uniformly throughout the nucleolus, directed by an intrinsic basic domain that targets it to nucleoli independently of complex assembly [#2, #6]. Functionally, knockdown of RPP38 causes accumulation of tRNA precursors, reduces RNase P activity in vitro, and coordinately lowers the levels of a subset of other RNase P protein subunits without affecting H1 RNA, indicating co-regulated expression of these subunits [#8, #9]. Unlike the RNase P subunits Rpp29 and Rpp21, RPP38 is not recruited to sites of DNA damage [#15].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Established that a 38 kDa polypeptide is a bona fide component of human RNase P, defining the protein composition of a previously RNA-centric enzyme.\",\n      \"evidence\": \"2000-fold biochemical purification of RNase P from HeLa cells with scleroderma serum immunodepletion, peptide sequencing, and cDNA cloning\",\n      \"pmids\": [\"9037013\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Copurification alone did not prove direct association with the active enzyme\", \"No RNA- or protein-binding partners identified\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Confirmed Rpp38 is an integral subunit of the catalytically active holoenzyme rather than a copurifying contaminant.\",\n      \"evidence\": \"Recombinant-protein-derived polyclonal antibodies immunoprecipitating active RNase P holoenzyme\",\n      \"pmids\": [\"9630247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define which RNA or proteins Rpp38 contacts within the complex\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Showed Rpp38 is shared between RNase P and RNase MRP and defined its nucleolar localization, linking it to two distinct processing enzymes.\",\n      \"evidence\": \"VSV-tagged co-immunoprecipitation of both complexes, UV crosslinking to MRP RNA nt 86-176, and immunofluorescence with a nucleolar-targeting reporter assay\",\n      \"pmids\": [\"10199568\", \"10444065\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the molecular determinant of complex selectivity\", \"Distinct from Rpp14/Rpp29 dense-fibrillar-component localization, but functional meaning unresolved\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Mapped Rpp38's molecular contacts—direct binding to H1 RNA and weak protein-protein interactions—and localized its nucleolar-targeting basic domain, building the architecture of the particle.\",\n      \"evidence\": \"Yeast three-hybrid and UV crosslinking for H1 RNA binding; yeast two-hybrid for inter-subunit contacts; GFP deletion mutants and co-IP for the basic nucleolar domain\",\n      \"pmids\": [\"11455963\", \"11158571\", \"11694598\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Two-hybrid interactions were weak and not all reciprocally validated\", \"Nucleolar targeting independent of complex association left functional rationale open\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Resolved the identity of the Th40 autoantigen as Rpp38 and corrected the prior assignment that Rpp38 binds the MRP P3 domain.\",\n      \"evidence\": \"Reconstitution and UV crosslinking with recombinant proteins and patient antisera\",\n      \"pmids\": [\"12483731\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The precise MRP RNA element bound by Rpp38 within the complex remained to be pinned down\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrated a functional requirement for Rpp38 in tRNA precursor processing and uncovered coordinate co-regulation of a subset of RNase P protein subunits.\",\n      \"evidence\": \"Stable overexpression, siRNA and EGS knockdown in HeLa cells with Northern blotting, in vitro RNase P activity assays, and RT-PCR/immunoblotting of other subunits\",\n      \"pmids\": [\"12907726\", \"12552092\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of coordinate subunit co-regulation not defined\", \"Whether processing defects are direct or secondary to subunit depletion unresolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Placed Rpp38 within an interaction map of the RNase MRP RNP, showing it directly binds both MRP RNA and multiple protein subunits.\",\n      \"evidence\": \"GST pull-down assays with recombinant subunits and MRP RNA fragment/deletion mutants\",\n      \"pmids\": [\"15096576\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Pull-down interactions not confirmed in the assembled holoenzyme\", \"Stoichiometry and spatial arrangement not determined\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Refined the picture of Rpp38 distribution across MRP complex states and the co-regulated subunit set.\",\n      \"evidence\": \"Glycerol gradient sedimentation and VSV-tagged co-IP across 12S and 60-80S MRP complexes; inducible EGS knockdown system\",\n      \"pmids\": [\"16723659\", \"16131590\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional difference between 12S and larger MRP complexes for Rpp38 unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Provided atomic-level mechanism for how Rpp38 recognizes its RNA target by solving the archaeal homologue bound to a K-turn motif.\",\n      \"evidence\": \"X-ray crystallography of PhoRpp38–SL12M (3.4 Å) with structure-based mutagenesis and pull-down validation\",\n      \"pmids\": [\"27114305\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure is of the archaeal homologue, not human RPP38\", \"K-turn binding by human RPP38 within its complexes not directly co-crystallized\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Distinguished Rpp38 from other RNase P subunits in moonlighting function by showing it is not recruited to DNA damage sites.\",\n      \"evidence\": \"Live-cell laser microirradiation imaging (negative result for Rpp38)\",\n      \"pmids\": [\"28432356\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not exclude DNA-damage roles under other conditions\", \"Negative result for a single recruitment readout\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended the structural basis of K-turn recognition and demonstrated Rpp38 assembly with neighboring subunits on an extended RNA stem-loop.\",\n      \"evidence\": \"Higher-resolution X-ray structures of PhoRpp38–K-turn complexes (2.1 Å, 3.1 Å) and co-purification of PhoRpp38/Rpp21/Rpp29 with P10-P12.2 RNA\",\n      \"pmids\": [\"29372908\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Archaeal system; human subassembly architecture not directly resolved\", \"Catalytic contribution of Rpp38 to substrate cleavage not addressed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPP38-mediated K-turn recognition is integrated into substrate selection and catalysis by the human RNase P and MRP holoenzymes, and the mechanism of coordinate co-regulation of RNase P subunits, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No human RPP38–RNA structure within the assembled holoenzyme\", \"Mechanism linking RPP38 depletion to loss of other subunits unknown\", \"Functional partition of RPP38 between RNase P and MRP roles undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [3, 5, 10, 14, 16]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [2, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 3, 8]}\n    ],\n    \"complexes\": [\"RNase P\", \"RNase MRP\"],\n    \"partners\": [\"POP1\", \"RPP40\", \"RPP30\", \"RPP29\", \"RPP21\", \"RPP20\", \"RPP25\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}