{"gene":"SNRNP35","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":2025,"finding":"SNRNP35 specifically recognizes U11 snRNA within the 13-subunit human U11 snRNP complex, as revealed by cryo-EM structures in apo and substrate-bound forms. SNRNP35 (along with SNRNP25) directly contacts U11 snRNA, while PDCD7 bridges SNRNP25 and SNRNP48 at the distal ends of the particle, and SNRNP48 and ZMAT5 stabilize binding of the incoming 5' splice site near the 5' end of U11 snRNA.","method":"Cryo-EM reconstruction of the human U11 snRNP complex in apo and substrate-bound forms (13-subunit complex)","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM structure with substrate-bound validation in a single rigorous study with multiple orthogonal structural states (apo and bound)","pmids":["39809272"],"is_preprint":false}],"current_model":"SNRNP35 is a minor spliceosome-specific factor that directly recognizes U11 snRNA within the human U11 snRNP complex, contributing to U12-type 5' splice site recognition during minor-class pre-mRNA splicing."},"narrative":{"mechanistic_narrative":"SNRNP35 is a subunit of the human U11 snRNP, a building block of the minor spliceosome that mediates U12-type pre-mRNA splicing [PMID:39809272]. Within the 13-subunit U11 snRNP, SNRNP35 directly contacts U11 snRNA, contributing to the structural organization of the particle that recognizes the incoming 5' splice site near the 5' end of U11 snRNA, where SNRNP48 and ZMAT5 stabilize substrate binding [PMID:39809272]. Beyond this structural role in U11 snRNA recognition defined by cryo-EM, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether and how SNRNP35 engages the minor spliceosome was unresolved; cryo-EM of the human U11 snRNP placed SNRNP35 in direct contact with U11 snRNA, establishing it as an snRNA-recognition subunit of the minor-class splicing machinery.","evidence":"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound states","pmids":["39809272"],"confidence":"High","gaps":["Functional consequence of SNRNP35 loss on minor-class splicing not tested","No biochemical dissection of SNRNP35's individual contribution to U11 snRNA binding versus the overall complex","No data on SNRNP35 outside the assembled U11 snRNP"]},{"year":null,"claim":"How SNRNP35 contributes functionally to 5' splice site recognition and minor-class splicing fidelity, and its behavior outside the structural complex, remain undefined.","evidence":"","pmids":[],"confidence":"High","gaps":["No perturbation/depletion studies linking SNRNP35 to splicing outcomes","No identification of SNRNP35 domains required for U11 snRNA binding"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0]}],"complexes":["U11 snRNP"],"partners":["SNRNP25","PDCD7","SNRNP48","ZMAT5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q16560","full_name":"U11/U12 small nuclear ribonucleoprotein 35 kDa protein","aliases":["Protein HM-1","U1 snRNP-binding protein homolog"],"length_aa":246,"mass_kda":29.4,"function":"","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q16560/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SNRNP35","classification":"Common Essential","n_dependent_lines":1206,"n_total_lines":1208,"dependency_fraction":0.9983443708609272},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SF3B1","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/SNRNP35","total_profiled":1310},"omim":[{"mim_id":"619631","title":"SMALL NUCLEAR RIBONUCLEOPROTEIN U11/U12, SUBUNIT 35; SNRNP35","url":"https://www.omim.org/entry/619631"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoli","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNRNP35"},"hgnc":{"alias_symbol":["U1SNRNPBP"],"prev_symbol":[]},"alphafold":{"accession":"Q16560","domains":[{"cath_id":"-","chopping":"1-39_137-164","consensus_level":"medium","plddt":88.8964,"start":1,"end":164},{"cath_id":"3.30.70.330","chopping":"43-133","consensus_level":"medium","plddt":94.1607,"start":43,"end":133}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q16560","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q16560-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q16560-F1-predicted_aligned_error_v6.png","plddt_mean":76.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNRNP35","jax_strain_url":"https://www.jax.org/strain/search?query=SNRNP35"},"sequence":{"accession":"Q16560","fasta_url":"https://rest.uniprot.org/uniprotkb/Q16560.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q16560/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q16560"}},"corpus_meta":[{"pmid":"22194820","id":"PMC_22194820","title":"Toxicogenomic and phenotypic analyses of bisphenol-A early-life exposure toxicity in zebrafish.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22194820","citation_count":94,"is_preprint":false},{"pmid":"36743888","id":"PMC_36743888","title":"Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library.","date":"2023","source":"Pharmacogenomics and personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36743888","citation_count":8,"is_preprint":false},{"pmid":"39809272","id":"PMC_39809272","title":"Structural basis of 5' splice site recognition by the minor spliceosome.","date":"2025","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/39809272","citation_count":7,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3938,"output_tokens":372,"usd":0.008697,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6592,"output_tokens":915,"usd":0.027918,"stage2_stop_reason":"end_turn"},"total_usd":0.036615,"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\": 2025,\n      \"finding\": \"SNRNP35 specifically recognizes U11 snRNA within the 13-subunit human U11 snRNP complex, as revealed by cryo-EM structures in apo and substrate-bound forms. SNRNP35 (along with SNRNP25) directly contacts U11 snRNA, while PDCD7 bridges SNRNP25 and SNRNP48 at the distal ends of the particle, and SNRNP48 and ZMAT5 stabilize binding of the incoming 5' splice site near the 5' end of U11 snRNA.\",\n      \"method\": \"Cryo-EM reconstruction of the human U11 snRNP complex in apo and substrate-bound forms (13-subunit complex)\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structure with substrate-bound validation in a single rigorous study with multiple orthogonal structural states (apo and bound)\",\n      \"pmids\": [\"39809272\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNRNP35 is a minor spliceosome-specific factor that directly recognizes U11 snRNA within the human U11 snRNP complex, contributing to U12-type 5' splice site recognition during minor-class pre-mRNA splicing.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNRNP35 is a subunit of the human U11 snRNP, a building block of the minor spliceosome that mediates U12-type pre-mRNA splicing [#0]. Within the 13-subunit U11 snRNP, SNRNP35 directly contacts U11 snRNA, contributing to the structural organization of the particle that recognizes the incoming 5' splice site near the 5' end of U11 snRNA, where SNRNP48 and ZMAT5 stabilize substrate binding [#0]. Beyond this structural role in U11 snRNA recognition defined by cryo-EM, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether and how SNRNP35 engages the minor spliceosome was unresolved; cryo-EM of the human U11 snRNP placed SNRNP35 in direct contact with U11 snRNA, establishing it as an snRNA-recognition subunit of the minor-class splicing machinery.\",\n      \"evidence\": \"Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound states\",\n      \"pmids\": [\"39809272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Functional consequence of SNRNP35 loss on minor-class splicing not tested\",\n        \"No biochemical dissection of SNRNP35's individual contribution to U11 snRNA binding versus the overall complex\",\n        \"No data on SNRNP35 outside the assembled U11 snRNP\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SNRNP35 contributes functionally to 5' splice site recognition and minor-class splicing fidelity, and its behavior outside the structural complex, remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No perturbation/depletion studies linking SNRNP35 to splicing outcomes\",\n        \"No identification of SNRNP35 domains required for U11 snRNA binding\"\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\": [\"SNRNP25\", \"PDCD7\", \"SNRNP48\", \"ZMAT5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":2,"faith_total":2,"faith_pct":100.0}}