{"gene":"RPP14","run_date":"2026-04-28T20:42:06","timeline":{"discoveries":[{"year":1999,"finding":"Rpp14 is a protein subunit of human ribonuclease P (RNase P) in HeLa cells; polyclonal antibodies against recombinant Rpp14 recognize its antigen in HeLa cells and precipitate catalytically active RNase P, establishing its association with the enzymatic complex.","method":"cDNA cloning, immunoprecipitation of catalytically active RNase P with polyclonal antibodies against recombinant Rpp14","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1-2 — direct immunoprecipitation of catalytically active RNase P complex confirmed by biochemical activity assay, single rigorous study","pmids":["10024167"],"is_preprint":false},{"year":2002,"finding":"Rpp14, a subunit of human RNase P, together with its interacting partner OIP2, possesses 3'→5' exoribonuclease activity with a phosphorolytic mechanism that processes the 3' terminus of precursor tRNA; purified RNase P alone lacks this exonuclease activity, indicating Rpp14/OIP2 constitute a distinct exosome-like activity.","method":"In vitro exoribonuclease assay, immunoprecipitation of Rpp14 and OIP2, biochemical fractionation of human RNase P complex","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 — in vitro enzymatic activity demonstrated directly with purified components plus controls showing purified RNase P lacks this activity","pmids":["11929972"],"is_preprint":false}],"current_model":"RPP14 (Rpp14) is a protein subunit of human RNase P that is required for catalytically active RNase P assembly, and together with its binding partner OIP2, possesses an intrinsic 3'→5' phosphorolytic exoribonuclease activity that processes the 3' terminus of precursor tRNA independently of the core RNase P endonuclease."},"narrative":{"teleology":[{"year":1999,"claim":"Establishing RPP14 as a bona fide RNase P subunit resolved its identity among the protein components of the human holoenzyme, showing it physically associates with a catalytically active complex.","evidence":"Immunoprecipitation of catalytically active RNase P from HeLa cell extracts using polyclonal antibodies raised against recombinant Rpp14","pmids":["10024167"],"confidence":"High","gaps":["Whether RPP14 contacts H1 RNA directly or is peripherally associated through other protein subunits was not determined","Stoichiometry of RPP14 within the holoenzyme was not established"]},{"year":2002,"claim":"Demonstrating that RPP14 and its partner OIP2 harbor a 3′→5′ phosphorolytic exoribonuclease activity for precursor tRNA 3′-end processing revealed a second catalytic function associated with, but distinct from, RNase P endonuclease activity.","evidence":"In vitro exoribonuclease assays with immunopurified RPP14–OIP2 complex and comparison to purified RNase P, which lacked exonuclease activity","pmids":["11929972"],"confidence":"High","gaps":["The relative contribution of RPP14 versus OIP2 to catalysis was not dissected","In vivo relevance of the exoribonuclease activity for tRNA maturation has not been demonstrated","Whether RPP14/OIP2 exonuclease activity extends to substrates beyond pre-tRNA is unknown"]},{"year":null,"claim":"It remains unknown how RPP14 coordinates its dual roles as an RNase P structural subunit and an exoribonuclease component, what its in vivo substrate scope is, and whether loss of RPP14 selectively disrupts tRNA 3′-end processing versus 5′-leader removal.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo loss-of-function or rescue studies have been reported","Structural basis for RPP14 integration into RNase P and interaction with OIP2 is unresolved","No disease association has been established through direct genetic evidence"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[1]}],"localization":[],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1]}],"complexes":["RNase P"],"partners":["OIP2"],"other_free_text":[]},"mechanistic_narrative":"RPP14 is a protein subunit of human ribonuclease P (RNase P), directly associating with the catalytically active holoenzyme complex in HeLa cells [PMID:10024167]. Beyond its structural role in RNase P, RPP14 together with its binding partner OIP2 possesses an intrinsic 3′→5′ phosphorolytic exoribonuclease activity that processes the 3′ terminus of precursor tRNA, an activity distinct from the endonucleolytic cleavage carried out by the RNase P core [PMID:11929972]."},"prefetch_data":{"uniprot":{"accession":"O95059","full_name":"Ribonuclease P protein subunit p14","aliases":[],"length_aa":124,"mass_kda":13.7,"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/O95059/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPP14","classification":"Common 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POP4","url":"https://www.omim.org/entry/606114"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":38.1},{"tissue":"tongue","ntpm":36.4}],"url":"https://www.proteinatlas.org/search/RPP14"},"hgnc":{"alias_symbol":["P14"],"prev_symbol":[]},"alphafold":{"accession":"O95059","domains":[{"cath_id":"3.30.70.3250","chopping":"32-107","consensus_level":"high","plddt":85.1018,"start":32,"end":107}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95059","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95059-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95059-F1-predicted_aligned_error_v6.png","plddt_mean":79.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPP14","jax_strain_url":"https://www.jax.org/strain/search?query=RPP14"},"sequence":{"accession":"O95059","fasta_url":"https://rest.uniprot.org/uniprotkb/O95059.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95059/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95059"}},"corpus_meta":[{"pmid":"9724636","id":"PMC_9724636","title":"The 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(New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — direct immunoprecipitation of catalytically active RNase P complex confirmed by biochemical activity assay, single rigorous study\",\n      \"pmids\": [\"10024167\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Rpp14, a subunit of human RNase P, together with its interacting partner OIP2, possesses 3'→5' exoribonuclease activity with a phosphorolytic mechanism that processes the 3' terminus of precursor tRNA; purified RNase P alone lacks this exonuclease activity, indicating Rpp14/OIP2 constitute a distinct exosome-like activity.\",\n      \"method\": \"In vitro exoribonuclease assay, immunoprecipitation of Rpp14 and OIP2, biochemical fractionation of human RNase P complex\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro enzymatic activity demonstrated directly with purified components plus controls showing purified RNase P lacks this activity\",\n      \"pmids\": [\"11929972\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPP14 (Rpp14) is a protein subunit of human RNase P that is required for catalytically active RNase P assembly, and together with its binding partner OIP2, possesses an intrinsic 3'→5' phosphorolytic exoribonuclease activity that processes the 3' terminus of precursor tRNA independently of the core RNase P endonuclease.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RPP14 is a protein subunit of human ribonuclease P (RNase P), directly associating with the catalytically active holoenzyme complex in HeLa cells [PMID:10024167]. Beyond its structural role in RNase P, RPP14 together with its binding partner OIP2 possesses an intrinsic 3′→5′ phosphorolytic exoribonuclease activity that processes the 3′ terminus of precursor tRNA, an activity distinct from the endonucleolytic cleavage carried out by the RNase P core [PMID:11929972].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Establishing RPP14 as a bona fide RNase P subunit resolved its identity among the protein components of the human holoenzyme, showing it physically associates with a catalytically active complex.\",\n      \"evidence\": \"Immunoprecipitation of catalytically active RNase P from HeLa cell extracts using polyclonal antibodies raised against recombinant Rpp14\",\n      \"pmids\": [\"10024167\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether RPP14 contacts H1 RNA directly or is peripherally associated through other protein subunits was not determined\",\n        \"Stoichiometry of RPP14 within the holoenzyme was not established\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Demonstrating that RPP14 and its partner OIP2 harbor a 3′→5′ phosphorolytic exoribonuclease activity for precursor tRNA 3′-end processing revealed a second catalytic function associated with, but distinct from, RNase P endonuclease activity.\",\n      \"evidence\": \"In vitro exoribonuclease assays with immunopurified RPP14–OIP2 complex and comparison to purified RNase P, which lacked exonuclease activity\",\n      \"pmids\": [\"11929972\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The relative contribution of RPP14 versus OIP2 to catalysis was not dissected\",\n        \"In vivo relevance of the exoribonuclease activity for tRNA maturation has not been demonstrated\",\n        \"Whether RPP14/OIP2 exonuclease activity extends to substrates beyond pre-tRNA is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how RPP14 coordinates its dual roles as an RNase P structural subunit and an exoribonuclease component, what its in vivo substrate scope is, and whether loss of RPP14 selectively disrupts tRNA 3′-end processing versus 5′-leader removal.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vivo loss-of-function or rescue studies have been reported\",\n        \"Structural basis for RPP14 integration into RNase P and interaction with OIP2 is unresolved\",\n        \"No disease association has been established through direct genetic evidence\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"RNase P\"],\n    \"partners\": [\"OIP2\"],\n    \"other_free_text\": []\n  }\n}\n```"}