{"gene":"POP4","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":1999,"finding":"Rpp29 (POP4) is a protein subunit of human RNase P; polyclonal antibodies against recombinant Rpp29 precipitate catalytically active RNase P from HeLa cells, establishing its presence in the active holoenzyme.","method":"cDNA cloning, immunoprecipitation of catalytically active RNase P with polyclonal antibodies against recombinant Rpp29","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal immunoprecipitation of active enzyme, single lab, two orthogonal methods (cloning + functional IP)","pmids":["10024167"],"is_preprint":false},{"year":2003,"finding":"The archaeal Rpp29 homolog (Mth11/Mth Rpp29) adopts an oligonucleotide/oligosaccharide binding (OB) fold with a structured beta-barrel core and flexible N- and C-terminal extensions; it is an essential protein component of the archaeal RNase P holoenzyme as shown by reconstitution, and contacts the RNase P RNA subunit as identified by NMR chemical shift perturbation.","method":"Solution NMR structure determination, reconstitution experiments with recombinant subunits, NMR chemical shift perturbation for protein-RNA interaction mapping","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — solution structure by NMR, reconstitution of holoenzyme activity, and RNA-interaction mapping by chemical shift perturbation in a single rigorous study","pmids":["14673079"],"is_preprint":false},{"year":2003,"finding":"The Archaeoglobus fulgidus Rpp29 homolog (an archaeal homolog of human Rpp29/yeast Pop4) forms a six-stranded antiparallel beta-sheet with flexible N- and C-terminal tails; conserved surface residues in the beta2-beta3 and beta4-beta5 loops and in the terminal tails are likely sites for RNA and protein interactions within RNase P.","method":"Multidimensional NMR structure determination, amide proton exchange, 15N relaxation rate measurements","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution NMR structure with dynamic characterization and sequence conservation analysis identifying functional surfaces","pmids":["14622001"],"is_preprint":false},{"year":2004,"finding":"The crystal structure of archaeal Rpp29 homolog Ph1771p reveals an OB-fold beta-barrel with topological similarity to RNA-binding proteins Hfq and L21E; two potential RNA-binding sites are identified: a concave surface with clustered positive charges (helices alpha1-alpha4 and strand beta6) and a loop (beta2-beta3) with conserved hydrophilic residues interacting with sulfate ion.","method":"X-ray crystallography at 2.0 Å resolution, structural comparison","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure at 2.0 Å with detailed identification of potential RNA-binding surfaces","pmids":["15317976"],"is_preprint":false},{"year":2008,"finding":"Human Rpp21 and Rpp29 bind each other, and together with catalytic H1 RNA are sufficient to activate endonucleolytic cleavage of precursor tRNA; the crystal structure of the archaeal PhoRpp21-PhoRpp29 heterodimer reveals that PhoRpp21's N-terminal helices (alpha1, alpha2) interact with PhoRpp29's N-terminal extended structure, beta-strand beta2, and C-terminal helix alpha3 via hydrogen bonds and salt bridges, forming a positively charged RNA-binding surface.","method":"Crystal structure determination of PhoRpp21-PhoRpp29 complex, mutational analysis, in vitro reconstitution of endonucleolytic cleavage activity","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure of protein complex combined with mutational analysis and reconstitution of RNase P activity","pmids":["18929577"],"is_preprint":false},{"year":2008,"finding":"The solution structure of Pyrococcus furiosus RPP21 and NMR chemical shift perturbations show that its two alpha-helices form the primary contact surface with RPP29, establishing the structural basis of RPP21-RPP29 interaction within the archaeal RNase P holoenzyme.","method":"Solution NMR structure determination, paramagnetic NMR, chemical shift perturbation analysis","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — NMR solution structure with chemical shift mapping of intermolecular contacts","pmids":["18922021"],"is_preprint":false},{"year":2009,"finding":"The solution NMR structure of the P. furiosus RPP21-RPP29 complex reveals a 30-kDa heterodimer formed by coupled folding of secondary structural elements at the interface; enzymatic footprinting localizes the RPP21-RPP29 complex to the specificity (S) domain of the RNase P RNA, and conserved basic surface residues are identified as likely contacts for RPR and/or pre-tRNA.","method":"Solution NMR structure of protein-protein complex, enzymatic footprinting, chemical shift perturbation","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — NMR complex structure with enzymatic footprinting to localize RNA contacts, multiple orthogonal methods","pmids":["19733182"],"is_preprint":false},{"year":2010,"finding":"Using chimeric RNase P RNAs composed of swapped C- and S-domains from E. coli M1 RNA and P. horikoshii PhopRNA, PhoRpp21 and PhoRpp29 (archaeal homologs of human Rpp21 and Rpp29) are shown to function in stabilization/activation of the PhopRNA S-domain (specificity domain), while PhoPop5 and PhoRpp30 function on the C-domain.","method":"Chimeric RNA construction, in vitro RNase P activity assays with purified protein subunits","journal":"Bioscience, biotechnology, and biochemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with chimeric RNAs, single lab","pmids":["20139629"],"is_preprint":false},{"year":2012,"finding":"Isothermal titration calorimetry of P. furiosus RPP21-RPP29 interaction reveals binding-coupled protein folding as a major thermodynamic contributor to complex formation (large negative heat capacity change), with a strong salt dependence and proton release at neutral pH; a folding-deficient RPP21 point mutant confirms that coupled folding drives the excess heat capacity change.","method":"Isothermal titration calorimetry (ITC), NMR spectroscopy, site-directed mutagenesis of RPP21","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — ITC with systematic thermodynamic dissection and mutagenesis, single lab with multiple orthogonal methods","pmids":["22243443"],"is_preprint":false},{"year":2016,"finding":"Rpp29 (along with Rpp21) is recruited to laser-microirradiated DNA damage sites in a PARP1-dependent manner by binding poly ADP-ribose moieties; depletion of Rpp29 and Rpp21 impairs homology-directed repair (HDR) of double-strand breaks but does not affect non-homologous end joining; additionally, depletion of the H1 RNA catalytic subunit diminishes their recruitment to damage sites, and RNase P activity is augmented after DNA damage in a PARP1-dependent manner.","method":"Laser microirradiation with live-cell imaging, siRNA knockdown, HDR and NHEJ reporter assays, poly ADP-ribose binding assays, RNase P activity assays after DNA damage","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (live imaging, activity assays, repair reporter assays, PAR binding), single lab","pmids":["28432356"],"is_preprint":false},{"year":2016,"finding":"Rpp29 is a component of an H3.3/RNA complex at transcriptionally active genomic loci; Rpp29 knockdown increases H3.3 chromatin incorporation at a reporter array, establishing Rpp29 as a repressor of H3.3 nucleosome deposition.","method":"Fluorescence live-cell imaging of tagged H3.3 at inducible transgene array, siRNA knockdown, co-localization analysis","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live-cell imaging with knockdown and quantitative H3.3 incorporation measurement, single lab","pmids":["26842893"],"is_preprint":false},{"year":2018,"finding":"Rpp29 directly interacts with histone H3.3 through a sequence element in its own N-terminus, and also interacts with histone H2B at an adjacent site (the N-terminal region is absent in archaeal Rpp29, suggesting eukaryote-specific evolution); Rpp29 represses H3.3 incorporation into transcriptionally active genes, represses mRNA/protein expression and antisense RNA, and promotes heterochromatic PTMs (H3K9me3, H3K27me3) while repressing euchromatic PTMs; oncogenic H3.3 mutations (G34V) alter the H3.3-Rpp29 interaction.","method":"Biochemical interaction assay (pull-down/co-IP with N-terminal truncations), Rpp29 knockdown in KNS42 (H3.3 G34V) glioma cells, ChIP for histone PTMs, RNA expression analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical interaction mapped to N-terminal domain combined with knockdown phenotyping for multiple histone PTMs, single lab","pmids":["29921582"],"is_preprint":false},{"year":2016,"finding":"Mutational analysis of PhoRpp21-PhoRpp29 complex shows that PhoRpp21 binds the P11-P12 loop in the PhopRNA S-domain via overall positive surface charges, while Lys53, Lys54, Lys56 in PhoRpp21's alpha2 helix and the 10 C-terminal residues of PhoRpp29 are essential for PhopRNA activation; PhoRpp29 alone has reduced affinity for PhopRNA compared to PhoRpp21, indicating PhoRpp21 is the primary RNA-binding element in the heterodimer.","method":"Pull-down assay for protein-RNA binding, site-directed mutagenesis of PhoRpp21 and PhoRpp29, in vitro RNase P activity assays with deletion mutants of PhopRNA","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pull-down plus mutagenesis plus activity assay, single lab","pmids":["27810361"],"is_preprint":false}],"current_model":"POP4/Rpp29 is a core protein subunit of the human RNase P ribonucleoprotein complex that adopts an OB-fold beta-barrel structure; it heterodimerizes with Rpp21 through coupled protein folding, and the Rpp21-Rpp29 pair binds the specificity (S) domain of the RNase P RNA to activate pre-tRNA 5'-leader cleavage; beyond tRNA processing, Rpp29 is recruited to DNA double-strand break sites via PARP1-dependent poly-ADP-ribose binding to promote homology-directed repair, and it represses H3.3 nucleosome deposition by directly binding H3.3 through its eukaryote-specific N-terminal extension."},"narrative":{"mechanistic_narrative":"POP4/Rpp29 is a core protein subunit of the human RNase P ribonucleoprotein endonuclease that drives 5'-leader cleavage of precursor tRNAs [PMID:10024167, PMID:18929577]. It adopts an OB-fold beta-barrel with flexible N- and C-terminal extensions and contacts the RNase P RNA subunit [PMID:14673079, PMID:18929577]. Functionally it acts as a heterodimer with Rpp21, whose assembly is driven by binding-coupled protein folding at the interface [PMID:22243443]; within this pair, Rpp21 supplies the primary positively charged RNA-binding surface while Rpp29's C-terminal residues are required for activation, and together they bind and stabilize the specificity (S) domain of the catalytic RNA to license pre-tRNA cleavage [PMID:19733182, PMID:27810361]. Beyond tRNA processing, Rpp29 has acquired eukaryote-specific roles: it is recruited to DNA double-strand break sites in a PARP1-dependent manner through poly(ADP-ribose) binding and is required for homology-directed repair but not non-homologous end joining [PMID:28432356], and it directly binds histone H3.3 through its eukaryote-specific N-terminal extension to repress H3.3 nucleosome deposition at active genes and to shape histone modification states [PMID:26842893, PMID:29921582].","teleology":[{"year":1999,"claim":"Established that Rpp29/POP4 is a bona fide protein subunit of the catalytically active human RNase P holoenzyme, not merely an associated factor.","evidence":"cDNA cloning and immunoprecipitation of active RNase P from HeLa cells with anti-Rpp29 antibodies","pmids":["10024167"],"confidence":"Medium","gaps":["Did not define the structure or RNA-contacting surface of Rpp29","No mechanistic role in catalysis assigned"]},{"year":2003,"claim":"Defined the fold of Rpp29 as an OB-fold beta-barrel with flexible terminal extensions and showed it is an essential, RNA-contacting subunit, providing the structural framework for its function.","evidence":"Solution/multidimensional NMR structures of archaeal Rpp29 homologs (Mth11, A. fulgidus), reconstitution, and chemical shift perturbation RNA mapping","pmids":["14673079","14622001"],"confidence":"High","gaps":["Used archaeal homologs rather than human Rpp29","Specific RNA contact residues not yet validated by mutagenesis"]},{"year":2004,"claim":"Identified candidate RNA-binding surfaces on the Rpp29 OB-fold by crystallography and linked the fold to known RNA-binding proteins.","evidence":"2.0 Å X-ray structure of archaeal Ph1771p with structural comparison and sulfate-ion binding analysis","pmids":["15317976"],"confidence":"High","gaps":["RNA-binding sites inferred from charge/conservation, not demonstrated functionally","Archaeal homolog only"]},{"year":2008,"claim":"Showed that Rpp21-Rpp29 heterodimerization plus the catalytic H1 RNA is sufficient to reconstitute pre-tRNA cleavage and resolved the atomic interface of the heterodimer.","evidence":"Crystal structure of archaeal PhoRpp21-PhoRpp29 complex, NMR of RPP21, mutational analysis, and in vitro cleavage reconstitution","pmids":["18929577","18922021"],"confidence":"High","gaps":["Did not localize the heterodimer on the RNA subunit","Thermodynamics of assembly unresolved"]},{"year":2009,"claim":"Localized the Rpp21-Rpp29 heterodimer to the specificity (S) domain of the RNase P RNA, defining where the pair acts on the catalytic RNA.","evidence":"Solution NMR structure of the P. furiosus RPP21-RPP29 complex with enzymatic footprinting and chemical shift perturbation","pmids":["19733182"],"confidence":"High","gaps":["Functional partition of S- vs C-domain roles between subunit pairs not yet tested","Human complex not directly mapped"]},{"year":2010,"claim":"Demonstrated functional division of labor in which the Rpp21-Rpp29 pair stabilizes/activates the S-domain while Pop5-Rpp30 acts on the C-domain.","evidence":"Chimeric C/S-domain RNase P RNAs reconstituted with purified archaeal protein subunits and activity assays","pmids":["20139629"],"confidence":"Medium","gaps":["Single lab, archaeal system","Residue-level basis of activation not yet defined"]},{"year":2012,"claim":"Established that Rpp29-Rpp21 complex formation is driven by binding-coupled protein folding, explaining the thermodynamics of assembly.","evidence":"Isothermal titration calorimetry with salt/pH dependence, NMR, and a folding-deficient RPP21 mutant","pmids":["22243443"],"confidence":"High","gaps":["Did not address human complex folding kinetics in vivo","No link to assembly chaperones"]},{"year":2016,"claim":"Refined the RNA-activation mechanism by showing Rpp21 supplies the primary RNA-binding surface while specific Rpp29 C-terminal residues are essential for S-domain activation.","evidence":"Pull-down RNA-binding assays, site-directed mutagenesis of PhoRpp21/PhoRpp29, and activity assays with PhopRNA deletion mutants","pmids":["27810361"],"confidence":"Medium","gaps":["Archaeal system; human residue requirements not confirmed","Single lab"]},{"year":2016,"claim":"Revealed a moonlighting role for Rpp29 in DNA double-strand break repair, linking RNase P subunits to PARP1-dependent genome maintenance.","evidence":"Laser microirradiation live imaging, PAR-binding assays, siRNA knockdown with HDR/NHEJ reporters, and post-damage RNase P activity assays","pmids":["28432356"],"confidence":"High","gaps":["Mechanism by which Rpp29 promotes HDR at the break is undefined","Whether the catalytic RNase P activity itself acts at breaks unresolved"]},{"year":2016,"claim":"Identified Rpp29 as a chromatin factor that represses H3.3 nucleosome deposition at transcriptionally active loci.","evidence":"Live-cell imaging of tagged H3.3 at an inducible transgene array with siRNA knockdown and co-localization","pmids":["26842893"],"confidence":"Medium","gaps":["Direct H3.3-binding interface not yet defined","Mechanism of deposition repression unclear"]},{"year":2018,"claim":"Mapped a direct, eukaryote-specific Rpp29-H3.3 interaction to its N-terminal extension and connected Rpp29 to histone PTM landscapes and oncogenic H3.3 mutations.","evidence":"Co-IP/pull-down with N-terminal truncations, Rpp29 knockdown in H3.3 G34V glioma cells, ChIP for histone PTMs, and RNA expression analysis","pmids":["29921582"],"confidence":"Medium","gaps":["Functional consequence of the G34V-altered interaction not mechanistically resolved","Relationship between chromatin role and RNase P catalytic role unclear","Single lab"]},{"year":null,"claim":"How Rpp29 partitions among its three roles — RNase P catalysis, PARP1-dependent DNA repair, and H3.3 chromatin regulation — and whether these activities are coordinated remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of the human heterodimer on human RNase P RNA","Mechanism linking PAR-binding recruitment to HDR not defined","Whether catalytic RNase P activity contributes to chromatin/repair functions unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1,4,6]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,4]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[10,11]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[4,6]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[9,10,11]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[9,10,11]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,4]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[9]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[10,11]}],"complexes":["RNase P","Rpp21-Rpp29 heterodimer"],"partners":["RPP21","H3.3","H2B","PARP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95707","full_name":"Ribonuclease P protein subunit p29","aliases":[],"length_aa":220,"mass_kda":25.4,"function":"Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/O95707/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/POP4","classification":"Common Essential","n_dependent_lines":1053,"n_total_lines":1208,"dependency_fraction":0.8716887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"RPP30","stoichiometry":4.0},{"gene":"DRG1","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2},{"gene":"SSB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/POP4","total_profiled":1310},"omim":[{"mim_id":"606114","title":"POP4 HOMOLOG, RIBONUCLEASE P/MRP SUBUNIT; POP4","url":"https://www.omim.org/entry/606114"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nucleoli","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/POP4"},"hgnc":{"alias_symbol":["RPP29"],"prev_symbol":[]},"alphafold":{"accession":"O95707","domains":[{"cath_id":"-","chopping":"12-53","consensus_level":"medium","plddt":79.7598,"start":12,"end":53},{"cath_id":"2.30.30.210","chopping":"96-220","consensus_level":"high","plddt":87.6822,"start":96,"end":220}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95707","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95707-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95707-F1-predicted_aligned_error_v6.png","plddt_mean":83.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=POP4","jax_strain_url":"https://www.jax.org/strain/search?query=POP4"},"sequence":{"accession":"O95707","fasta_url":"https://rest.uniprot.org/uniprotkb/O95707.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95707/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95707"}},"corpus_meta":[{"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":"14673079","id":"PMC_14673079","title":"Structure of Mth11/Mth Rpp29, an essential protein subunit of archaeal and eukaryotic RNase P.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/14673079","citation_count":40,"is_preprint":false},{"pmid":"19733182","id":"PMC_19733182","title":"Solution structure of an archaeal RNase P binary protein complex: formation of the 30-kDa complex between Pyrococcus furiosus RPP21 and RPP29 is accompanied by coupled protein folding and highlights critical features for protein-protein and protein-RNA interactions.","date":"2009","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19733182","citation_count":34,"is_preprint":false},{"pmid":"18929577","id":"PMC_18929577","title":"Structure of an archaeal homolog of the human protein complex Rpp21-Rpp29 that is a key core component for the assembly of active ribonuclease P.","date":"2008","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/18929577","citation_count":34,"is_preprint":false},{"pmid":"15317976","id":"PMC_15317976","title":"Crystal structure of archaeal ribonuclease P protein Ph1771p from Pyrococcus horikoshii OT3: an archaeal homolog of eukaryotic ribonuclease P protein Rpp29.","date":"2004","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/15317976","citation_count":32,"is_preprint":false},{"pmid":"28432356","id":"PMC_28432356","title":"A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28432356","citation_count":26,"is_preprint":false},{"pmid":"14622001","id":"PMC_14622001","title":"NMR structure of an archaeal homologue of ribonuclease P protein Rpp29.","date":"2003","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14622001","citation_count":26,"is_preprint":false},{"pmid":"26842893","id":"PMC_26842893","title":"RNase P protein subunit Rpp29 represses histone H3.3 nucleosome deposition.","date":"2016","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/26842893","citation_count":24,"is_preprint":false},{"pmid":"18922021","id":"PMC_18922021","title":"Solution structure of Pyrococcus furiosus RPP21, a component of the archaeal RNase P holoenzyme, and interactions with its RPP29 protein partner.","date":"2008","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18922021","citation_count":19,"is_preprint":false},{"pmid":"20139629","id":"PMC_20139629","title":"Archaeal homologs of human RNase P protein pairs Pop5 with Rpp30 and Rpp21 with Rpp29 work on distinct functional domains of the RNA subunit.","date":"2010","source":"Bioscience, biotechnology, and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20139629","citation_count":18,"is_preprint":false},{"pmid":"29921582","id":"PMC_29921582","title":"Rpp29 regulates histone H3.3 chromatin assembly through transcriptional mechanisms.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29921582","citation_count":16,"is_preprint":false},{"pmid":"15351636","id":"PMC_15351636","title":"Inhibition of the expression of the human RNase P protein subunits Rpp21, Rpp25, Rpp29 by external guide sequences (EGSs) and siRNA.","date":"2004","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15351636","citation_count":16,"is_preprint":false},{"pmid":"22243443","id":"PMC_22243443","title":"Thermodynamics of coupled folding in the interaction of archaeal RNase P proteins RPP21 and RPP29.","date":"2012","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22243443","citation_count":9,"is_preprint":false},{"pmid":"12699688","id":"PMC_12699688","title":"Preparation of uniformly labeled NMR samples in Escherichia coli under the tight control of the araBAD promoter: expression of an archaeal homolog of the RNase P Rpp29 protein.","date":"2003","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/12699688","citation_count":8,"is_preprint":false},{"pmid":"27810361","id":"PMC_27810361","title":"Functional characterization of archaeal homologs of human nuclear RNase P proteins Rpp21 and Rpp29 provides insights into the molecular basis of their cooperativity in catalysis.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/27810361","citation_count":2,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.10.30.621158","title":"In a model of parasite-mediated exhaustion, stem-like CD8 T cells differentiate into an unconventional intermediate effector memory subset","date":"2024-11-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.30.621158","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9667,"output_tokens":3452,"usd":0.040391,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11032,"output_tokens":3706,"usd":0.073905,"stage2_stop_reason":"end_turn"},"total_usd":0.114296,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"Rpp29 (POP4) is a protein subunit of human RNase P; polyclonal antibodies against recombinant Rpp29 precipitate catalytically active RNase P from HeLa cells, establishing its presence in the active holoenzyme.\",\n      \"method\": \"cDNA cloning, immunoprecipitation of catalytically active RNase P with polyclonal antibodies against recombinant Rpp29\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal immunoprecipitation of active enzyme, single lab, two orthogonal methods (cloning + functional IP)\",\n      \"pmids\": [\"10024167\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The archaeal Rpp29 homolog (Mth11/Mth Rpp29) adopts an oligonucleotide/oligosaccharide binding (OB) fold with a structured beta-barrel core and flexible N- and C-terminal extensions; it is an essential protein component of the archaeal RNase P holoenzyme as shown by reconstitution, and contacts the RNase P RNA subunit as identified by NMR chemical shift perturbation.\",\n      \"method\": \"Solution NMR structure determination, reconstitution experiments with recombinant subunits, NMR chemical shift perturbation for protein-RNA interaction mapping\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — solution structure by NMR, reconstitution of holoenzyme activity, and RNA-interaction mapping by chemical shift perturbation in a single rigorous study\",\n      \"pmids\": [\"14673079\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The Archaeoglobus fulgidus Rpp29 homolog (an archaeal homolog of human Rpp29/yeast Pop4) forms a six-stranded antiparallel beta-sheet with flexible N- and C-terminal tails; conserved surface residues in the beta2-beta3 and beta4-beta5 loops and in the terminal tails are likely sites for RNA and protein interactions within RNase P.\",\n      \"method\": \"Multidimensional NMR structure determination, amide proton exchange, 15N relaxation rate measurements\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution NMR structure with dynamic characterization and sequence conservation analysis identifying functional surfaces\",\n      \"pmids\": [\"14622001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The crystal structure of archaeal Rpp29 homolog Ph1771p reveals an OB-fold beta-barrel with topological similarity to RNA-binding proteins Hfq and L21E; two potential RNA-binding sites are identified: a concave surface with clustered positive charges (helices alpha1-alpha4 and strand beta6) and a loop (beta2-beta3) with conserved hydrophilic residues interacting with sulfate ion.\",\n      \"method\": \"X-ray crystallography at 2.0 Å resolution, structural comparison\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure at 2.0 Å with detailed identification of potential RNA-binding surfaces\",\n      \"pmids\": [\"15317976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Human Rpp21 and Rpp29 bind each other, and together with catalytic H1 RNA are sufficient to activate endonucleolytic cleavage of precursor tRNA; the crystal structure of the archaeal PhoRpp21-PhoRpp29 heterodimer reveals that PhoRpp21's N-terminal helices (alpha1, alpha2) interact with PhoRpp29's N-terminal extended structure, beta-strand beta2, and C-terminal helix alpha3 via hydrogen bonds and salt bridges, forming a positively charged RNA-binding surface.\",\n      \"method\": \"Crystal structure determination of PhoRpp21-PhoRpp29 complex, mutational analysis, in vitro reconstitution of endonucleolytic cleavage activity\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure of protein complex combined with mutational analysis and reconstitution of RNase P activity\",\n      \"pmids\": [\"18929577\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The solution structure of Pyrococcus furiosus RPP21 and NMR chemical shift perturbations show that its two alpha-helices form the primary contact surface with RPP29, establishing the structural basis of RPP21-RPP29 interaction within the archaeal RNase P holoenzyme.\",\n      \"method\": \"Solution NMR structure determination, paramagnetic NMR, chemical shift perturbation analysis\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — NMR solution structure with chemical shift mapping of intermolecular contacts\",\n      \"pmids\": [\"18922021\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The solution NMR structure of the P. furiosus RPP21-RPP29 complex reveals a 30-kDa heterodimer formed by coupled folding of secondary structural elements at the interface; enzymatic footprinting localizes the RPP21-RPP29 complex to the specificity (S) domain of the RNase P RNA, and conserved basic surface residues are identified as likely contacts for RPR and/or pre-tRNA.\",\n      \"method\": \"Solution NMR structure of protein-protein complex, enzymatic footprinting, chemical shift perturbation\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — NMR complex structure with enzymatic footprinting to localize RNA contacts, multiple orthogonal methods\",\n      \"pmids\": [\"19733182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Using chimeric RNase P RNAs composed of swapped C- and S-domains from E. coli M1 RNA and P. horikoshii PhopRNA, PhoRpp21 and PhoRpp29 (archaeal homologs of human Rpp21 and Rpp29) are shown to function in stabilization/activation of the PhopRNA S-domain (specificity domain), while PhoPop5 and PhoRpp30 function on the C-domain.\",\n      \"method\": \"Chimeric RNA construction, in vitro RNase P activity assays with purified protein subunits\",\n      \"journal\": \"Bioscience, biotechnology, and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with chimeric RNAs, single lab\",\n      \"pmids\": [\"20139629\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Isothermal titration calorimetry of P. furiosus RPP21-RPP29 interaction reveals binding-coupled protein folding as a major thermodynamic contributor to complex formation (large negative heat capacity change), with a strong salt dependence and proton release at neutral pH; a folding-deficient RPP21 point mutant confirms that coupled folding drives the excess heat capacity change.\",\n      \"method\": \"Isothermal titration calorimetry (ITC), NMR spectroscopy, site-directed mutagenesis of RPP21\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — ITC with systematic thermodynamic dissection and mutagenesis, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"22243443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Rpp29 (along with Rpp21) is recruited to laser-microirradiated DNA damage sites in a PARP1-dependent manner by binding poly ADP-ribose moieties; depletion of Rpp29 and Rpp21 impairs homology-directed repair (HDR) of double-strand breaks but does not affect non-homologous end joining; additionally, depletion of the H1 RNA catalytic subunit diminishes their recruitment to damage sites, and RNase P activity is augmented after DNA damage in a PARP1-dependent manner.\",\n      \"method\": \"Laser microirradiation with live-cell imaging, siRNA knockdown, HDR and NHEJ reporter assays, poly ADP-ribose binding assays, RNase P activity assays after DNA damage\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (live imaging, activity assays, repair reporter assays, PAR binding), single lab\",\n      \"pmids\": [\"28432356\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Rpp29 is a component of an H3.3/RNA complex at transcriptionally active genomic loci; Rpp29 knockdown increases H3.3 chromatin incorporation at a reporter array, establishing Rpp29 as a repressor of H3.3 nucleosome deposition.\",\n      \"method\": \"Fluorescence live-cell imaging of tagged H3.3 at inducible transgene array, siRNA knockdown, co-localization analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live-cell imaging with knockdown and quantitative H3.3 incorporation measurement, single lab\",\n      \"pmids\": [\"26842893\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Rpp29 directly interacts with histone H3.3 through a sequence element in its own N-terminus, and also interacts with histone H2B at an adjacent site (the N-terminal region is absent in archaeal Rpp29, suggesting eukaryote-specific evolution); Rpp29 represses H3.3 incorporation into transcriptionally active genes, represses mRNA/protein expression and antisense RNA, and promotes heterochromatic PTMs (H3K9me3, H3K27me3) while repressing euchromatic PTMs; oncogenic H3.3 mutations (G34V) alter the H3.3-Rpp29 interaction.\",\n      \"method\": \"Biochemical interaction assay (pull-down/co-IP with N-terminal truncations), Rpp29 knockdown in KNS42 (H3.3 G34V) glioma cells, ChIP for histone PTMs, RNA expression analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical interaction mapped to N-terminal domain combined with knockdown phenotyping for multiple histone PTMs, single lab\",\n      \"pmids\": [\"29921582\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Mutational analysis of PhoRpp21-PhoRpp29 complex shows that PhoRpp21 binds the P11-P12 loop in the PhopRNA S-domain via overall positive surface charges, while Lys53, Lys54, Lys56 in PhoRpp21's alpha2 helix and the 10 C-terminal residues of PhoRpp29 are essential for PhopRNA activation; PhoRpp29 alone has reduced affinity for PhopRNA compared to PhoRpp21, indicating PhoRpp21 is the primary RNA-binding element in the heterodimer.\",\n      \"method\": \"Pull-down assay for protein-RNA binding, site-directed mutagenesis of PhoRpp21 and PhoRpp29, in vitro RNase P activity assays with deletion mutants of PhopRNA\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pull-down plus mutagenesis plus activity assay, single lab\",\n      \"pmids\": [\"27810361\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"POP4/Rpp29 is a core protein subunit of the human RNase P ribonucleoprotein complex that adopts an OB-fold beta-barrel structure; it heterodimerizes with Rpp21 through coupled protein folding, and the Rpp21-Rpp29 pair binds the specificity (S) domain of the RNase P RNA to activate pre-tRNA 5'-leader cleavage; beyond tRNA processing, Rpp29 is recruited to DNA double-strand break sites via PARP1-dependent poly-ADP-ribose binding to promote homology-directed repair, and it represses H3.3 nucleosome deposition by directly binding H3.3 through its eukaryote-specific N-terminal extension.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"POP4/Rpp29 is a core protein subunit of the human RNase P ribonucleoprotein endonuclease that drives 5'-leader cleavage of precursor tRNAs [#0, #4]. It adopts an OB-fold beta-barrel with flexible N- and C-terminal extensions and contacts the RNase P RNA subunit [#1, #4]. Functionally it acts as a heterodimer with Rpp21, whose assembly is driven by binding-coupled protein folding at the interface [#8]; within this pair, Rpp21 supplies the primary positively charged RNA-binding surface while Rpp29's C-terminal residues are required for activation, and together they bind and stabilize the specificity (S) domain of the catalytic RNA to license pre-tRNA cleavage [#6, #12]. Beyond tRNA processing, Rpp29 has acquired eukaryote-specific roles: it is recruited to DNA double-strand break sites in a PARP1-dependent manner through poly(ADP-ribose) binding and is required for homology-directed repair but not non-homologous end joining [#9], and it directly binds histone H3.3 through its eukaryote-specific N-terminal extension to repress H3.3 nucleosome deposition at active genes and to shape histone modification states [#10, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established that Rpp29/POP4 is a bona fide protein subunit of the catalytically active human RNase P holoenzyme, not merely an associated factor.\",\n      \"evidence\": \"cDNA cloning and immunoprecipitation of active RNase P from HeLa cells with anti-Rpp29 antibodies\",\n      \"pmids\": [\"10024167\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not define the structure or RNA-contacting surface of Rpp29\", \"No mechanistic role in catalysis assigned\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Defined the fold of Rpp29 as an OB-fold beta-barrel with flexible terminal extensions and showed it is an essential, RNA-contacting subunit, providing the structural framework for its function.\",\n      \"evidence\": \"Solution/multidimensional NMR structures of archaeal Rpp29 homologs (Mth11, A. fulgidus), reconstitution, and chemical shift perturbation RNA mapping\",\n      \"pmids\": [\"14673079\", \"14622001\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Used archaeal homologs rather than human Rpp29\", \"Specific RNA contact residues not yet validated by mutagenesis\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Identified candidate RNA-binding surfaces on the Rpp29 OB-fold by crystallography and linked the fold to known RNA-binding proteins.\",\n      \"evidence\": \"2.0 Å X-ray structure of archaeal Ph1771p with structural comparison and sulfate-ion binding analysis\",\n      \"pmids\": [\"15317976\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"RNA-binding sites inferred from charge/conservation, not demonstrated functionally\", \"Archaeal homolog only\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showed that Rpp21-Rpp29 heterodimerization plus the catalytic H1 RNA is sufficient to reconstitute pre-tRNA cleavage and resolved the atomic interface of the heterodimer.\",\n      \"evidence\": \"Crystal structure of archaeal PhoRpp21-PhoRpp29 complex, NMR of RPP21, mutational analysis, and in vitro cleavage reconstitution\",\n      \"pmids\": [\"18929577\", \"18922021\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not localize the heterodimer on the RNA subunit\", \"Thermodynamics of assembly unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Localized the Rpp21-Rpp29 heterodimer to the specificity (S) domain of the RNase P RNA, defining where the pair acts on the catalytic RNA.\",\n      \"evidence\": \"Solution NMR structure of the P. furiosus RPP21-RPP29 complex with enzymatic footprinting and chemical shift perturbation\",\n      \"pmids\": [\"19733182\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional partition of S- vs C-domain roles between subunit pairs not yet tested\", \"Human complex not directly mapped\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrated functional division of labor in which the Rpp21-Rpp29 pair stabilizes/activates the S-domain while Pop5-Rpp30 acts on the C-domain.\",\n      \"evidence\": \"Chimeric C/S-domain RNase P RNAs reconstituted with purified archaeal protein subunits and activity assays\",\n      \"pmids\": [\"20139629\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single lab, archaeal system\", \"Residue-level basis of activation not yet defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that Rpp29-Rpp21 complex formation is driven by binding-coupled protein folding, explaining the thermodynamics of assembly.\",\n      \"evidence\": \"Isothermal titration calorimetry with salt/pH dependence, NMR, and a folding-deficient RPP21 mutant\",\n      \"pmids\": [\"22243443\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not address human complex folding kinetics in vivo\", \"No link to assembly chaperones\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Refined the RNA-activation mechanism by showing Rpp21 supplies the primary RNA-binding surface while specific Rpp29 C-terminal residues are essential for S-domain activation.\",\n      \"evidence\": \"Pull-down RNA-binding assays, site-directed mutagenesis of PhoRpp21/PhoRpp29, and activity assays with PhopRNA deletion mutants\",\n      \"pmids\": [\"27810361\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Archaeal system; human residue requirements not confirmed\", \"Single lab\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Revealed a moonlighting role for Rpp29 in DNA double-strand break repair, linking RNase P subunits to PARP1-dependent genome maintenance.\",\n      \"evidence\": \"Laser microirradiation live imaging, PAR-binding assays, siRNA knockdown with HDR/NHEJ reporters, and post-damage RNase P activity assays\",\n      \"pmids\": [\"28432356\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism by which Rpp29 promotes HDR at the break is undefined\", \"Whether the catalytic RNase P activity itself acts at breaks unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified Rpp29 as a chromatin factor that represses H3.3 nucleosome deposition at transcriptionally active loci.\",\n      \"evidence\": \"Live-cell imaging of tagged H3.3 at an inducible transgene array with siRNA knockdown and co-localization\",\n      \"pmids\": [\"26842893\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct H3.3-binding interface not yet defined\", \"Mechanism of deposition repression unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapped a direct, eukaryote-specific Rpp29-H3.3 interaction to its N-terminal extension and connected Rpp29 to histone PTM landscapes and oncogenic H3.3 mutations.\",\n      \"evidence\": \"Co-IP/pull-down with N-terminal truncations, Rpp29 knockdown in H3.3 G34V glioma cells, ChIP for histone PTMs, and RNA expression analysis\",\n      \"pmids\": [\"29921582\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional consequence of the G34V-altered interaction not mechanistically resolved\", \"Relationship between chromatin role and RNase P catalytic role unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How Rpp29 partitions among its three roles — RNase P catalysis, PARP1-dependent DNA repair, and H3.3 chromatin regulation — and whether these activities are coordinated remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No structure of the human heterodimer on human RNase P RNA\", \"Mechanism linking PAR-binding recruitment to HDR not defined\", \"Whether catalytic RNase P activity contributes to chromatin/repair functions unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1, 4, 6]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [10, 11]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [9, 10, 11]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [9, 10, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [10, 11]}\n    ],\n    \"complexes\": [\n      \"RNase P\",\n      \"Rpp21-Rpp29 heterodimer\"\n    ],\n    \"partners\": [\n      \"RPP21\",\n      \"H3.3\",\n      \"H2B\",\n      \"PARP1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":4,"faith_total":4,"faith_pct":100.0}}