{"gene":"RRP36","run_date":"2026-06-10T07:46:28","timeline":{"discoveries":[{"year":2009,"finding":"Rrp36p is a nucleolar protein that associates with 90S and pre-40S preribosomal particles; its depletion in yeast causes defects in early cleavages of the 35S pre-rRNA and a rapid decrease in mature 18S rRNA levels, establishing its role in small subunit (40S) biogenesis.","method":"Genetic depletion (conditional knockdown), northern blotting, sucrose-gradient sedimentation/co-fractionation with preribosomal particles, nucleolar localization by microscopy","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (depletion phenotype, fractionation, localization) in a single focused study, with functional conservation validated in human HeLa cells","pmids":["20038530"],"is_preprint":false},{"year":2009,"finding":"Rrp36p is a novel component of the 90S preribosome; its recruitment depends on the UTP-A and UTP-B modules (depletion of UTP-A or UTP-B components prevents Rrp36p association and reduces its accumulation), but depletion of Rrp5p does not prevent Rrp36p recruitment. Conversely, Rrp36p depletion does not impair incorporation of the tUTP/UTP-A, PWP2/UTP-B, or UTP-C subcomplexes, nor U3 snoRNP, into preribosomes.","method":"Epistasis/order-of-assembly analysis by depletion of individual components followed by co-fractionation and western blotting of preribosomal particles","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal depletion epistasis with multiple assembly factors, single focused study with rigorous controls","pmids":["20038530"],"is_preprint":false},{"year":2009,"finding":"The function of Rrp36 in early pre-rRNA cleavages is evolutionarily conserved: depletion of the human orthologue (C6orf153/RRP36) in HeLa cells also impairs early pre-rRNA processing.","method":"siRNA knockdown in HeLa cells followed by northern blotting of pre-rRNA intermediates","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockdown with defined rRNA processing readout, single lab, limited to abstract-level detail on human data","pmids":["20038530"],"is_preprint":false},{"year":2020,"finding":"Rrp36 directly interacts with the β-propeller domain of Rrp9 (U3-55K) within the SSU-processome; this interaction is weakened by the R289A substitution in Rrp9, which also specifically reduces pre-rRNA cleavage at sites A1 and A2, implicating the Rrp9–Rrp36 interaction in SSU-processome function.","method":"Protein-protein interaction mapping (direct interaction assay), site-directed mutagenesis of Rrp9 (R289A), pre-rRNA processing analysis by northern blotting","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct interaction identified and disrupted by mutagenesis with corresponding processing phenotype, single lab study","pmids":["31996908"],"is_preprint":false}],"current_model":"RRP36 is an essential nucleolar protein and novel component of the 90S preribosome whose recruitment depends on the UTP-A and UTP-B assembly modules; it is required for early pre-rRNA cleavages that produce the 18S rRNA and the 40S ribosomal subunit, directly interacts with the Rrp9/U3-55K β-propeller domain within the SSU-processome, and this function is conserved from yeast to human cells."},"narrative":{"mechanistic_narrative":"RRP36 (Rrp36p) is an essential nucleolar protein required for the early pre-rRNA cleavages that generate the 18S rRNA and the small (40S) ribosomal subunit [PMID:20038530]. It associates with 90S and pre-40S preribosomal particles, and its depletion blocks early cleavages of the 35S pre-rRNA and rapidly depletes mature 18S rRNA [PMID:20038530]. Within the SSU-processome, RRP36 is recruited as a function of the UTP-A and UTP-B assembly modules, while it is itself dispensable for incorporation of the UTP-A, UTP-B, UTP-C subcomplexes and the U3 snoRNP, placing it downstream of these modules in the assembly hierarchy [PMID:20038530]. RRP36 directly contacts the β-propeller domain of Rrp9 (U3-55K), and disruption of this interface specifically impairs cleavage at sites A1 and A2, linking the Rrp9–RRP36 contact to processome function [PMID:31996908]. This role in early pre-rRNA processing is conserved to the human orthologue (C6orf153/RRP36) [PMID:20038530].","teleology":[{"year":2009,"claim":"Established that Rrp36p is a nucleolar factor functionally required for small subunit biogenesis, answering whether the uncharacterized protein had a defined role in ribosome assembly.","evidence":"Conditional depletion, northern blotting of pre-rRNA, sucrose-gradient co-fractionation, and nucleolar localization in yeast","pmids":["20038530"],"confidence":"High","gaps":["Molecular activity of Rrp36 during cleavage not defined","Does not establish whether Rrp36 acts catalytically or as a scaffold"]},{"year":2009,"claim":"Positioned Rrp36 in the 90S preribosome assembly hierarchy, resolving which modules license its recruitment versus which depend on it.","evidence":"Reciprocal depletion epistasis with UTP-A, UTP-B, UTP-C, U3 snoRNP and Rrp5p followed by co-fractionation and western blotting","pmids":["20038530"],"confidence":"High","gaps":["Direct binding partner mediating UTP-A/UTP-B-dependent recruitment not identified at this stage","Structural basis of incorporation unknown"]},{"year":2009,"claim":"Tested whether the processing role is conserved beyond yeast, addressing relevance of the yeast findings to human ribosome biogenesis.","evidence":"siRNA knockdown of human C6orf153/RRP36 in HeLa cells with northern analysis of pre-rRNA intermediates","pmids":["20038530"],"confidence":"Medium","gaps":["Human data limited to processing readout","Human interaction partners and assembly context not mapped"]},{"year":2020,"claim":"Identified a direct molecular contact (Rrp9 β-propeller) explaining how Rrp36 is integrated into the SSU-processome and contributes to specific cleavages.","evidence":"Direct interaction assay, site-directed mutagenesis of Rrp9 (R289A), and northern analysis of A1/A2 cleavage in yeast","pmids":["31996908"],"confidence":"Medium","gaps":["Single lab study","Atomic structure of the Rrp36-Rrp9 interface not solved","Whether this contact alone accounts for UTP-A/UTP-B-dependent recruitment unresolved"]},{"year":null,"claim":"The biochemical activity of RRP36 within the processome — whether it directly facilitates cleavage chemistry, conformational rearrangement, or substrate positioning — remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No catalytic activity assigned","No structural model of RRP36 in the processome","Human interactome not characterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2]}],"complexes":["90S preribosome / SSU-processome","pre-40S particle"],"partners":["RRP9"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96EU6","full_name":"Ribosomal RNA processing protein 36 homolog","aliases":[],"length_aa":259,"mass_kda":29.8,"function":"Involved in the early processing steps of the pre-rRNA in the maturation pathway leading to the 18S rRNA","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q96EU6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RRP36","classification":"Not Classified","n_dependent_lines":167,"n_total_lines":1208,"dependency_fraction":0.1382450331125828},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000124541","cell_line_id":"CID001612","localizations":[{"compartment":"nucleolus_gc","grade":3},{"compartment":"nucleoplasm","grade":2},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"ARF5","stoichiometry":0.2},{"gene":"GAR1","stoichiometry":0.2},{"gene":"LMNB1","stoichiometry":0.2},{"gene":"SRP19","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001612","total_profiled":1310},"omim":[{"mim_id":"613475","title":"RIBOSOMAL RNA-PROCESSING 36; RRP36","url":"https://www.omim.org/entry/613475"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Nucleoli","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RRP36"},"hgnc":{"alias_symbol":["dJ20C7.4"],"prev_symbol":["C6orf153"]},"alphafold":{"accession":"Q96EU6","domains":[{"cath_id":"1.20.58","chopping":"131-212","consensus_level":"medium","plddt":94.238,"start":131,"end":212},{"cath_id":"1.20.5","chopping":"213-252","consensus_level":"medium","plddt":94.115,"start":213,"end":252}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96EU6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96EU6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96EU6-F1-predicted_aligned_error_v6.png","plddt_mean":81.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RRP36","jax_strain_url":"https://www.jax.org/strain/search?query=RRP36"},"sequence":{"accession":"Q96EU6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96EU6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96EU6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96EU6"}},"corpus_meta":[{"pmid":"15983380","id":"PMC_15983380","title":"Complex humoral immune response against a benign tumor: frequent antibody response against specific antigens as diagnostic targets.","date":"2005","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/15983380","citation_count":68,"is_preprint":false},{"pmid":"20038530","id":"PMC_20038530","title":"Evolutionarily conserved function of RRP36 in early cleavages of the pre-rRNA and production of the 40S ribosomal subunit.","date":"2009","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/20038530","citation_count":25,"is_preprint":false},{"pmid":"31996908","id":"PMC_31996908","title":"Synergistic defects in pre-rRNA processing from mutations in the U3-specific protein Rrp9 and U3 snoRNA.","date":"2020","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31996908","citation_count":22,"is_preprint":false},{"pmid":"38698449","id":"PMC_38698449","title":"The effects of exosomes originating from different cell sources on the differentiation of bone marrow mesenchymal stem cells into schwann cells.","date":"2024","source":"Journal of nanobiotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/38698449","citation_count":9,"is_preprint":false},{"pmid":"35601016","id":"PMC_35601016","title":"Multiomics Integrated Analysis Identifies SLC24A2 as a Potential Link between Type 2 Diabetes and Cancer.","date":"2022","source":"Journal of diabetes research","url":"https://pubmed.ncbi.nlm.nih.gov/35601016","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5451,"output_tokens":1121,"usd":0.016584,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7626,"output_tokens":1633,"usd":0.039477,"stage2_stop_reason":"end_turn"},"total_usd":0.056061,"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\": 2009,\n      \"finding\": \"Rrp36p is a nucleolar protein that associates with 90S and pre-40S preribosomal particles; its depletion in yeast causes defects in early cleavages of the 35S pre-rRNA and a rapid decrease in mature 18S rRNA levels, establishing its role in small subunit (40S) biogenesis.\",\n      \"method\": \"Genetic depletion (conditional knockdown), northern blotting, sucrose-gradient sedimentation/co-fractionation with preribosomal particles, nucleolar localization by microscopy\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (depletion phenotype, fractionation, localization) in a single focused study, with functional conservation validated in human HeLa cells\",\n      \"pmids\": [\"20038530\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Rrp36p is a novel component of the 90S preribosome; its recruitment depends on the UTP-A and UTP-B modules (depletion of UTP-A or UTP-B components prevents Rrp36p association and reduces its accumulation), but depletion of Rrp5p does not prevent Rrp36p recruitment. Conversely, Rrp36p depletion does not impair incorporation of the tUTP/UTP-A, PWP2/UTP-B, or UTP-C subcomplexes, nor U3 snoRNP, into preribosomes.\",\n      \"method\": \"Epistasis/order-of-assembly analysis by depletion of individual components followed by co-fractionation and western blotting of preribosomal particles\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal depletion epistasis with multiple assembly factors, single focused study with rigorous controls\",\n      \"pmids\": [\"20038530\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The function of Rrp36 in early pre-rRNA cleavages is evolutionarily conserved: depletion of the human orthologue (C6orf153/RRP36) in HeLa cells also impairs early pre-rRNA processing.\",\n      \"method\": \"siRNA knockdown in HeLa cells followed by northern blotting of pre-rRNA intermediates\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown with defined rRNA processing readout, single lab, limited to abstract-level detail on human data\",\n      \"pmids\": [\"20038530\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Rrp36 directly interacts with the β-propeller domain of Rrp9 (U3-55K) within the SSU-processome; this interaction is weakened by the R289A substitution in Rrp9, which also specifically reduces pre-rRNA cleavage at sites A1 and A2, implicating the Rrp9–Rrp36 interaction in SSU-processome function.\",\n      \"method\": \"Protein-protein interaction mapping (direct interaction assay), site-directed mutagenesis of Rrp9 (R289A), pre-rRNA processing analysis by northern blotting\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct interaction identified and disrupted by mutagenesis with corresponding processing phenotype, single lab study\",\n      \"pmids\": [\"31996908\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RRP36 is an essential nucleolar protein and novel component of the 90S preribosome whose recruitment depends on the UTP-A and UTP-B assembly modules; it is required for early pre-rRNA cleavages that produce the 18S rRNA and the 40S ribosomal subunit, directly interacts with the Rrp9/U3-55K β-propeller domain within the SSU-processome, and this function is conserved from yeast to human cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RRP36 (Rrp36p) is an essential nucleolar protein required for the early pre-rRNA cleavages that generate the 18S rRNA and the small (40S) ribosomal subunit [#0]. It associates with 90S and pre-40S preribosomal particles, and its depletion blocks early cleavages of the 35S pre-rRNA and rapidly depletes mature 18S rRNA [#0]. Within the SSU-processome, RRP36 is recruited as a function of the UTP-A and UTP-B assembly modules, while it is itself dispensable for incorporation of the UTP-A, UTP-B, UTP-C subcomplexes and the U3 snoRNP, placing it downstream of these modules in the assembly hierarchy [#1]. RRP36 directly contacts the β-propeller domain of Rrp9 (U3-55K), and disruption of this interface specifically impairs cleavage at sites A1 and A2, linking the Rrp9–RRP36 contact to processome function [#3]. This role in early pre-rRNA processing is conserved to the human orthologue (C6orf153/RRP36) [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established that Rrp36p is a nucleolar factor functionally required for small subunit biogenesis, answering whether the uncharacterized protein had a defined role in ribosome assembly.\",\n      \"evidence\": \"Conditional depletion, northern blotting of pre-rRNA, sucrose-gradient co-fractionation, and nucleolar localization in yeast\",\n      \"pmids\": [\"20038530\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular activity of Rrp36 during cleavage not defined\", \"Does not establish whether Rrp36 acts catalytically or as a scaffold\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Positioned Rrp36 in the 90S preribosome assembly hierarchy, resolving which modules license its recruitment versus which depend on it.\",\n      \"evidence\": \"Reciprocal depletion epistasis with UTP-A, UTP-B, UTP-C, U3 snoRNP and Rrp5p followed by co-fractionation and western blotting\",\n      \"pmids\": [\"20038530\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding partner mediating UTP-A/UTP-B-dependent recruitment not identified at this stage\", \"Structural basis of incorporation unknown\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Tested whether the processing role is conserved beyond yeast, addressing relevance of the yeast findings to human ribosome biogenesis.\",\n      \"evidence\": \"siRNA knockdown of human C6orf153/RRP36 in HeLa cells with northern analysis of pre-rRNA intermediates\",\n      \"pmids\": [\"20038530\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Human data limited to processing readout\", \"Human interaction partners and assembly context not mapped\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified a direct molecular contact (Rrp9 β-propeller) explaining how Rrp36 is integrated into the SSU-processome and contributes to specific cleavages.\",\n      \"evidence\": \"Direct interaction assay, site-directed mutagenesis of Rrp9 (R289A), and northern analysis of A1/A2 cleavage in yeast\",\n      \"pmids\": [\"31996908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab study\", \"Atomic structure of the Rrp36-Rrp9 interface not solved\", \"Whether this contact alone accounts for UTP-A/UTP-B-dependent recruitment unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of RRP36 within the processome — whether it directly facilitates cleavage chemistry, conformational rearrangement, or substrate positioning — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No catalytic activity assigned\", \"No structural model of RRP36 in the processome\", \"Human interactome not characterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\"90S preribosome / SSU-processome\", \"pre-40S particle\"],\n    \"partners\": [\"RRP9\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}