{"gene":"SNRNP48","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2004,"finding":"SNRNP48 (U11-48K) was identified as a novel protein component of the human 18S U11/U12 di-snRNP and 12S U11 snRNP, not found in the major spliceosome. Mass spectrometry analysis showed it is one of four proteins (59K, 48K, 35K, 25K) specifically associated with the U11 snRNP within the di-snRNP complex. RNAi knockdown of U11/U12 proteins including 48K revealed they are essential for cell viability, indicating a key role in U12-type splicing.","method":"Affinity purification of U11/U12 snRNPs followed by mass spectrometry; RNAi knockdown with cell viability readout","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 — reciprocal purification + MS identification + functional RNAi validation, moderate evidence","pmids":["15146077"],"is_preprint":false},{"year":2008,"finding":"SNRNP48 (U11-48K) directly contacts the 5' splice site (5'ss) of U12-type introns via site-specific RNA-protein cross-linking. This interaction is sequence-dependent and sensitive to 5'ss mutations. 48K also interacts with the U11-59K protein. RNAi-mediated knockdown of 48K inhibited U12-type splicing, activated cryptic U2-type splice sites, reduced cell growth, and decreased U11/U12 di-snRNP levels, indicating 48K is critical for U12-type intron recognition and di-snRNP stability.","method":"Site-specific RNA-protein cross-linking; RNAi knockdown with splicing assays and cell growth readouts; co-immunoprecipitation for protein-protein interaction","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (cross-linking, RNAi + splicing assay, co-IP) in a single study with rigorous controls","pmids":["18347052"],"is_preprint":false},{"year":2009,"finding":"The solution structure of the SNRNP48 (U11-48K) CHHC zinc-finger domain was determined by NMR. The domain shows unexpected structural similarity to TFIIIA-type zinc fingers, with distinct features from its zinc-coordinating residues (CHHC). The CHHC Zn-finger specifically binds the 5' splice site sequence of U12-type introns when base-paired to U11 snRNA in vitro, suggesting it stabilizes U11–5'ss base-pairing and contributes to minor spliceosome assembly.","method":"NMR solution structure determination; in vitro RNA binding assay with U12-type 5'ss sequences","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 — NMR structure with functional in vitro binding validation","pmids":["19217400"],"is_preprint":false},{"year":2024,"finding":"Cryo-EM structure of the fully assembled human minor spliceosome pre-B complex at 3.3 Å resolution revealed that U11 snRNA is recognized by five U11-specific proteins including SNRNP48 (U11-48K). The 5' half of the 5'-splice site is recognized jointly by U11-35K, U11-48K, and U11 snRNA, providing structural detail of 5'ss recognition within the assembled minor spliceosome.","method":"Cryo-electron microscopy (3.3 Å resolution) with atomic model building","journal":"Science (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 — high-resolution cryo-EM structure with atomic model of protein-RNA interactions","pmids":["38484052"],"is_preprint":false},{"year":2025,"finding":"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms revealed that SNRNP48 is positioned near the 5' end of U11 snRNA and stabilizes binding of the incoming U12-type 5' splice site. PDCD7 bridges SNRNP25 and SNRNP48, which are located at distal ends of the particle. SNRNP48 and ZMAT5 together participate in 5'SS recognition, which is achieved through base-pairing to U11 snRNA and non-canonical base-triple interactions with U11 snRNA stem-loop 3.","method":"Cryo-electron microscopy reconstruction of apo and substrate-bound U11 snRNP","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structures in both apo and substrate-bound states, revealing molecular mechanism of 5'SS recognition","pmids":["39809272"],"is_preprint":false}],"current_model":"SNRNP48 (U11-48K) is a U11 snRNP-specific protein of the minor spliceosome whose CHHC zinc-finger domain directly contacts U12-type 5' splice sites in a sequence-dependent manner, stabilizing U11 snRNA–5'SS base-pairing; it interacts with U11-59K and is bridged to SNRNP25 via PDCD7 within the U11 particle, and is essential for U12-type intron recognition, U11/U12 di-snRNP stability, and cell viability."},"narrative":{"teleology":[{"year":2004,"claim":"Establishing the molecular identity of minor spliceosome-specific subunits resolved which proteins are dedicated to U12-type splicing: SNRNP48 was identified as one of four U11 snRNP-specific proteins absent from the major spliceosome, and knockdown showed it is required for cell viability.","evidence":"Affinity purification of human U11/U12 di-snRNP followed by mass spectrometry and RNAi-mediated knockdown with viability readout","pmids":["15146077"],"confidence":"High","gaps":["Molecular function of SNRNP48 within the U11 particle was unknown","Direct RNA contacts had not been mapped","Whether SNRNP48 loss specifically impairs U12-type splicing or has broader effects was not distinguished"]},{"year":2008,"claim":"Defining how the minor spliceosome recognizes U12-type 5' splice sites, cross-linking demonstrated that SNRNP48 directly and sequence-dependently contacts the 5'SS, interacts with U11-59K, and is required for U12-type intron splicing and U11/U12 di-snRNP stability.","evidence":"Site-specific RNA-protein cross-linking, co-immunoprecipitation, and RNAi knockdown with RT-PCR splicing assays in human cells","pmids":["18347052"],"confidence":"High","gaps":["The structural basis for sequence-dependent 5'SS recognition was not resolved","Whether 48K recognizes the 5'SS alone or cooperatively with other subunits was unclear"]},{"year":2009,"claim":"Determining how the SNRNP48 CHHC zinc-finger domain achieves RNA recognition, NMR structure determination revealed an unexpected TFIIIA-type fold that specifically binds the U11 snRNA–5'SS duplex, establishing this domain as the structural basis for stabilizing splice-site base-pairing.","evidence":"NMR solution structure of the CHHC zinc-finger domain and in vitro RNA binding assays with U12-type 5'SS sequences","pmids":["19217400"],"confidence":"High","gaps":["How this interaction is positioned within the intact U11 snRNP particle was unknown","Contribution of other U11 proteins to cooperative 5'SS recognition was not addressed"]},{"year":2024,"claim":"Placing SNRNP48 into the architectural context of an assembled minor spliceosome, the cryo-EM structure of the pre-B complex showed that U11-48K, together with U11-35K and U11 snRNA, jointly recognizes the 5' half of the 5' splice site at atomic resolution.","evidence":"Cryo-EM of the human minor spliceosome pre-B complex at 3.3 Å resolution with atomic model building","pmids":["38484052"],"confidence":"High","gaps":["The apo-state architecture of U11 snRNP before substrate engagement was not captured","The role of PDCD7 in organizing the U11 particle was not resolved"]},{"year":2025,"claim":"Resolving the complete U11 snRNP in both apo and substrate-bound states clarified that SNRNP48 is positioned near the 5' end of U11 snRNA, is bridged to SNRNP25 by PDCD7, and cooperates with ZMAT5 in 5'SS recognition through non-canonical base-triple interactions with U11 snRNA stem-loop 3.","evidence":"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms","pmids":["39809272"],"confidence":"High","gaps":["Conformational dynamics of SNRNP48 during spliceosome activation and catalysis are not captured","How disease-associated mutations in minor spliceosome genes affect SNRNP48 function is unexplored"]},{"year":null,"claim":"It remains unknown how SNRNP48's interactions are remodeled during the transition from early U11 recognition to catalytic activation of U12-type introns, and whether SNRNP48 participates in regulatory discrimination among U12-type substrates.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural data for SNRNP48 in activated or catalytic spliceosome states","Potential regulatory roles in alternative splicing of U12-type introns are uncharacterized","No in vivo structure–function analysis of the CHHC zinc-finger domain"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1,2,3,4]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,4]}],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0,3,4]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,3,4]}],"complexes":["U11 snRNP","U11/U12 di-snRNP","Minor spliceosome (pre-B complex)"],"partners":["SNRNP35","SNRNP25","PDCD7","ZMAT5","RNPC3"],"other_free_text":[]},"mechanistic_narrative":"SNRNP48 (U11-48K) is a U11 snRNP-specific protein of the minor (U12-dependent) spliceosome that is essential for recognition of U12-type 5' splice sites and cell viability [PMID:15146077, PMID:18347052]. Its CHHC zinc-finger domain, structurally related to TFIIIA-type zinc fingers, directly contacts the 5' splice site sequence in a sequence-dependent manner and stabilizes U11 snRNA–5'SS base-pairing [PMID:19217400, PMID:18347052]. Within the U11 snRNP particle, SNRNP48 is bridged to SNRNP25 via PDCD7 and cooperates with U11-35K and ZMAT5 in 5'SS recognition through canonical base-pairing and non-canonical base-triple interactions with U11 snRNA stem-loop 3 [PMID:38484052, PMID:39809272]. Depletion of SNRNP48 inhibits U12-type splicing, activates cryptic U2-type splice sites, and destabilizes the U11/U12 di-snRNP [PMID:18347052]."},"prefetch_data":{"uniprot":{"accession":"Q6IEG0","full_name":"U11/U12 small nuclear ribonucleoprotein 48 kDa protein","aliases":[],"length_aa":339,"mass_kda":40.0,"function":"Likely involved in U12-type 5' splice site recognition","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q6IEG0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SNRNP48","classification":"Not Classified","n_dependent_lines":516,"n_total_lines":1208,"dependency_fraction":0.4271523178807947},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ELOVL6","stoichiometry":0.2},{"gene":"SF3B1","stoichiometry":0.2},{"gene":"SF3B6","stoichiometry":0.2},{"gene":"SNRPB","stoichiometry":0.2},{"gene":"SNRPD2","stoichiometry":0.2},{"gene":"SNRPF","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SNRNP48","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNRNP48"},"hgnc":{"alias_symbol":["FLJ32234","dJ512B11.2","dJ336K20B.1"],"prev_symbol":["C6orf151"]},"alphafold":{"accession":"Q6IEG0","domains":[{"cath_id":"-","chopping":"56-93","consensus_level":"high","plddt":87.3208,"start":56,"end":93},{"cath_id":"-","chopping":"104-179","consensus_level":"high","plddt":82.623,"start":104,"end":179},{"cath_id":"-","chopping":"191-241","consensus_level":"medium","plddt":72.12,"start":191,"end":241},{"cath_id":"1.20.5","chopping":"9-44","consensus_level":"high","plddt":87.8539,"start":9,"end":44}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6IEG0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6IEG0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6IEG0-F1-predicted_aligned_error_v6.png","plddt_mean":71.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNRNP48","jax_strain_url":"https://www.jax.org/strain/search?query=SNRNP48"},"sequence":{"accession":"Q6IEG0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6IEG0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6IEG0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6IEG0"}},"corpus_meta":[{"pmid":"33691721","id":"PMC_33691721","title":"Integrative 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alliance","url":"https://pubmed.ncbi.nlm.nih.gov/35914814","citation_count":6,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2654,"output_tokens":364,"usd":0.006711},"stage2":{"model":"claude-opus-4-6","input_tokens":3510,"output_tokens":738,"usd":0.054},"total_usd":0.203424,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":15127,"output_tokens":1536,"usd":0.03421},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5022,"output_tokens":1889,"usd":0.108503}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structures of the human U11 snRNP complex reveal that SNRNP48 is positioned near the 5' end of U11 snRNA, where it stabilizes binding of the incoming 5' splice site (5'SS) during U12-type intron recognition by the minor spliceosome. PDCD7 bridges SNRNP25 and SNRNP48, which are located at the distal ends of the particle.\",\n      \"method\": \"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure in apo and substrate-bound states with architectural and mechanistic detail\",\n      \"pmids\": [\"39809272\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNRNP48 is a component of the human U11 snRNP complex of the minor spliceosome, positioned near the 5' end of U11 snRNA where it stabilizes 5' splice site binding during U12-type intron recognition, and is connected to the rest of the particle via PDCD7, which bridges SNRNP48 and SNRNP25 at distal ends of the complex.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"SNRNP48 (U11-48K) was identified as a novel protein component of the human 18S U11/U12 di-snRNP and 12S U11 snRNP, not found in the major spliceosome. Mass spectrometry analysis showed it is one of four proteins (59K, 48K, 35K, 25K) specifically associated with the U11 snRNP within the di-snRNP complex. RNAi knockdown of U11/U12 proteins including 48K revealed they are essential for cell viability, indicating a key role in U12-type splicing.\",\n      \"method\": \"Affinity purification of U11/U12 snRNPs followed by mass spectrometry; RNAi knockdown with cell viability readout\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal purification + MS identification + functional RNAi validation, moderate evidence\",\n      \"pmids\": [\"15146077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"SNRNP48 (U11-48K) directly contacts the 5' splice site (5'ss) of U12-type introns via site-specific RNA-protein cross-linking. This interaction is sequence-dependent and sensitive to 5'ss mutations. 48K also interacts with the U11-59K protein. RNAi-mediated knockdown of 48K inhibited U12-type splicing, activated cryptic U2-type splice sites, reduced cell growth, and decreased U11/U12 di-snRNP levels, indicating 48K is critical for U12-type intron recognition and di-snRNP stability.\",\n      \"method\": \"Site-specific RNA-protein cross-linking; RNAi knockdown with splicing assays and cell growth readouts; co-immunoprecipitation for protein-protein interaction\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (cross-linking, RNAi + splicing assay, co-IP) in a single study with rigorous controls\",\n      \"pmids\": [\"18347052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The solution structure of the SNRNP48 (U11-48K) CHHC zinc-finger domain was determined by NMR. The domain shows unexpected structural similarity to TFIIIA-type zinc fingers, with distinct features from its zinc-coordinating residues (CHHC). The CHHC Zn-finger specifically binds the 5' splice site sequence of U12-type introns when base-paired to U11 snRNA in vitro, suggesting it stabilizes U11–5'ss base-pairing and contributes to minor spliceosome assembly.\",\n      \"method\": \"NMR solution structure determination; in vitro RNA binding assay with U12-type 5'ss sequences\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — NMR structure with functional in vitro binding validation\",\n      \"pmids\": [\"19217400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Cryo-EM structure of the fully assembled human minor spliceosome pre-B complex at 3.3 Å resolution revealed that U11 snRNA is recognized by five U11-specific proteins including SNRNP48 (U11-48K). The 5' half of the 5'-splice site is recognized jointly by U11-35K, U11-48K, and U11 snRNA, providing structural detail of 5'ss recognition within the assembled minor spliceosome.\",\n      \"method\": \"Cryo-electron microscopy (3.3 Å resolution) with atomic model building\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — high-resolution cryo-EM structure with atomic model of protein-RNA interactions\",\n      \"pmids\": [\"38484052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms revealed that SNRNP48 is positioned near the 5' end of U11 snRNA and stabilizes binding of the incoming U12-type 5' splice site. PDCD7 bridges SNRNP25 and SNRNP48, which are located at distal ends of the particle. SNRNP48 and ZMAT5 together participate in 5'SS recognition, which is achieved through base-pairing to U11 snRNA and non-canonical base-triple interactions with U11 snRNA stem-loop 3.\",\n      \"method\": \"Cryo-electron microscopy reconstruction of apo and substrate-bound U11 snRNP\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structures in both apo and substrate-bound states, revealing molecular mechanism of 5'SS recognition\",\n      \"pmids\": [\"39809272\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNRNP48 (U11-48K) is a U11 snRNP-specific protein of the minor spliceosome whose CHHC zinc-finger domain directly contacts U12-type 5' splice sites in a sequence-dependent manner, stabilizing U11 snRNA–5'SS base-pairing; it interacts with U11-59K and is bridged to SNRNP25 via PDCD7 within the U11 particle, and is essential for U12-type intron recognition, U11/U12 di-snRNP stability, and cell viability.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SNRNP48 is a subunit of the human U11 snRNP complex of the minor spliceosome, positioned near the 5' end of U11 snRNA where it stabilizes binding of the incoming 5' splice site during U12-type intron recognition [PMID:39809272]. Within the 13-subunit U11 snRNP particle, PDCD7 bridges SNRNP48 and SNRNP25, which occupy distal ends of the complex, thereby connecting SNRNP48 to the rest of the particle [PMID:39809272].\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Cryo-EM structures resolved the architectural position and functional role of SNRNP48 within the U11 snRNP, establishing that it resides near the 5' end of U11 snRNA and stabilizes 5' splice site recognition during U12-type intron processing.\",\n      \"evidence\": \"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms\",\n      \"pmids\": [\"39809272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No mutagenesis or depletion data demonstrating which residues or domains of SNRNP48 are essential for 5'SS stabilization\",\n        \"The mechanism by which SNRNP48 is recruited to U11 snRNP during particle assembly is unknown\",\n        \"Whether SNRNP48 has additional roles at later steps of minor spliceosome catalysis has not been examined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how SNRNP48 contributes to the transition from U11 snRNP recognition to catalytically active minor spliceosome assembly, and whether it has functions beyond 5'SS stabilization.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional assays (e.g., splicing reconstitution, knockdown/knockout) have been reported for SNRNP48 specifically\",\n        \"No disease-associated variants in SNRNP48 have been characterized\",\n        \"Structural dynamics of SNRNP48 during the transition from U11 to U11/U12 di-snRNP are unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"U11 snRNP\"],\n    \"partners\": [\"PDCD7\", \"SNRNP25\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"SNRNP48 (U11-48K) is a U11 snRNP-specific protein of the minor (U12-dependent) spliceosome that is essential for recognition of U12-type 5' splice sites and cell viability [PMID:15146077, PMID:18347052]. Its CHHC zinc-finger domain, structurally related to TFIIIA-type zinc fingers, directly contacts the 5' splice site sequence in a sequence-dependent manner and stabilizes U11 snRNA–5'SS base-pairing [PMID:19217400, PMID:18347052]. Within the U11 snRNP particle, SNRNP48 is bridged to SNRNP25 via PDCD7 and cooperates with U11-35K and ZMAT5 in 5'SS recognition through canonical base-pairing and non-canonical base-triple interactions with U11 snRNA stem-loop 3 [PMID:38484052, PMID:39809272]. Depletion of SNRNP48 inhibits U12-type splicing, activates cryptic U2-type splice sites, and destabilizes the U11/U12 di-snRNP [PMID:18347052].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing the molecular identity of minor spliceosome-specific subunits resolved which proteins are dedicated to U12-type splicing: SNRNP48 was identified as one of four U11 snRNP-specific proteins absent from the major spliceosome, and knockdown showed it is required for cell viability.\",\n      \"evidence\": \"Affinity purification of human U11/U12 di-snRNP followed by mass spectrometry and RNAi-mediated knockdown with viability readout\",\n      \"pmids\": [\"15146077\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular function of SNRNP48 within the U11 particle was unknown\",\n        \"Direct RNA contacts had not been mapped\",\n        \"Whether SNRNP48 loss specifically impairs U12-type splicing or has broader effects was not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defining how the minor spliceosome recognizes U12-type 5' splice sites, cross-linking demonstrated that SNRNP48 directly and sequence-dependently contacts the 5'SS, interacts with U11-59K, and is required for U12-type intron splicing and U11/U12 di-snRNP stability.\",\n      \"evidence\": \"Site-specific RNA-protein cross-linking, co-immunoprecipitation, and RNAi knockdown with RT-PCR splicing assays in human cells\",\n      \"pmids\": [\"18347052\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The structural basis for sequence-dependent 5'SS recognition was not resolved\",\n        \"Whether 48K recognizes the 5'SS alone or cooperatively with other subunits was unclear\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Determining how the SNRNP48 CHHC zinc-finger domain achieves RNA recognition, NMR structure determination revealed an unexpected TFIIIA-type fold that specifically binds the U11 snRNA–5'SS duplex, establishing this domain as the structural basis for stabilizing splice-site base-pairing.\",\n      \"evidence\": \"NMR solution structure of the CHHC zinc-finger domain and in vitro RNA binding assays with U12-type 5'SS sequences\",\n      \"pmids\": [\"19217400\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How this interaction is positioned within the intact U11 snRNP particle was unknown\",\n        \"Contribution of other U11 proteins to cooperative 5'SS recognition was not addressed\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placing SNRNP48 into the architectural context of an assembled minor spliceosome, the cryo-EM structure of the pre-B complex showed that U11-48K, together with U11-35K and U11 snRNA, jointly recognizes the 5' half of the 5' splice site at atomic resolution.\",\n      \"evidence\": \"Cryo-EM of the human minor spliceosome pre-B complex at 3.3 Å resolution with atomic model building\",\n      \"pmids\": [\"38484052\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The apo-state architecture of U11 snRNP before substrate engagement was not captured\",\n        \"The role of PDCD7 in organizing the U11 particle was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolving the complete U11 snRNP in both apo and substrate-bound states clarified that SNRNP48 is positioned near the 5' end of U11 snRNA, is bridged to SNRNP25 by PDCD7, and cooperates with ZMAT5 in 5'SS recognition through non-canonical base-triple interactions with U11 snRNA stem-loop 3.\",\n      \"evidence\": \"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms\",\n      \"pmids\": [\"39809272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Conformational dynamics of SNRNP48 during spliceosome activation and catalysis are not captured\",\n        \"How disease-associated mutations in minor spliceosome genes affect SNRNP48 function is unexplored\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how SNRNP48's interactions are remodeled during the transition from early U11 recognition to catalytic activation of U12-type introns, and whether SNRNP48 participates in regulatory discrimination among U12-type substrates.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural data for SNRNP48 in activated or catalytic spliceosome states\",\n        \"Potential regulatory roles in alternative splicing of U12-type introns are uncharacterized\",\n        \"No in vivo structure–function analysis of the CHHC zinc-finger domain\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1, 2, 3, 4]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0, 3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 3, 4]}\n    ],\n    \"complexes\": [\n      \"U11 snRNP\",\n      \"U11/U12 di-snRNP\",\n      \"Minor spliceosome (pre-B complex)\"\n    ],\n    \"partners\": [\n      \"SNRNP35\",\n      \"SNRNP25\",\n      \"PDCD7\",\n      \"ZMAT5\",\n      \"RNPC3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}