{"gene":"SNRNP25","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2025,"finding":"Cryo-EM structures of the 13-subunit human U11 snRNP complex revealed that SNRNP25 specifically recognizes U11 snRNA and that PDCD7 bridges SNRNP25 and SNRNP48, which are located at the distal ends of the particle, establishing the architectural role of SNRNP25 within the minor spliceosome.","method":"Cryo-EM reconstruction of apo and substrate-bound human U11 snRNP complex","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure with functional validation of RNA and protein interactions in a single rigorous study","pmids":["39809272"],"is_preprint":false},{"year":2025,"finding":"SNRNP25 loss (via the Hbab2(th) deletion in mouse) is identified as the candidate gene most likely responsible for peri-implantation lethality in homozygous mice, indicating SNRNP25 is essential for early mammalian development.","method":"Molecular deletion mapping, sequence analysis, and expression analysis of Hbab2(th) mouse deletion spanning the Snrnp25 locus","journal":"Mammalian genome","confidence":"Medium","confidence_rationale":"Tier 2 — genetic/genomic mapping with molecular analysis, but candidate status not yet confirmed by rescue experiment","pmids":["40399475"],"is_preprint":false},{"year":2014,"finding":"The LRP1-SNRNP25 fusion gene (formed by fusion of LRP1 and SNRNP25 sequences) promotes migration and invasion of SAOS-2 osteosarcoma cells, as demonstrated by overexpression experiments.","method":"Transcriptome sequencing, RT-PCR, Sanger sequencing, FISH validation, and cell migration/invasion assays with LRP1-SNRNP25 overexpression in SAOS-2 cells","journal":"Journal of hematology & oncology","confidence":"Medium","confidence_rationale":"Tier 2 — functional overexpression with multiple orthogonal validation methods, but involves a fusion protein not wild-type SNRNP25","pmids":["25300797"],"is_preprint":false},{"year":2024,"finding":"The LRP1-SNRNP25 fusion protein (LRP1 exon 8 fused to SNRNP25 exon 2) promotes osteosarcoma cell invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway; co-IP demonstrated that LRP1-SNRNP25 physically interacts with pJNK and 37LRP proteins, and 37LRP knockdown reduced MMP2 levels downstream.","method":"Whole-genome sequencing, scratch/Transwell assays, western blotting, co-immunoprecipitation-mass spectrometry, co-IP, immunofluorescence, siRNA knockdown, pJNK inhibitor (SP600125) treatment, and in vivo xenograft with immunohistochemistry","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods including co-IP, epistasis by inhibitor/siRNA, and in vivo validation; involves fusion protein context","pmids":["38678020"],"is_preprint":false}],"current_model":"SNRNP25 is a component of the human U11 snRNP of the minor spliceosome, where it specifically recognizes U11 snRNA and is bridged to SNRNP48 via PDCD7 at the distal end of the particle, contributing to U12-type 5' splice site recognition; loss of Snrnp25 in mice is associated with peri-implantation lethality, while a recurrent LRP1-SNRNP25 fusion in osteosarcoma drives cell invasion and migration through the pJNK/37LRP/MMP2 signaling pathway."},"narrative":{"teleology":[{"year":2014,"claim":"Identification of a recurrent LRP1-SNRNP25 fusion gene in osteosarcoma established that SNRNP25 participates in oncogenic gene fusions and that the fusion product promotes tumor cell migration and invasion.","evidence":"Transcriptome sequencing, RT-PCR, FISH validation, and overexpression migration/invasion assays in SAOS-2 osteosarcoma cells","pmids":["25300797"],"confidence":"Medium","gaps":["Mechanism involves a fusion protein, not wild-type SNRNP25, so the contribution of SNRNP25 sequences to oncogenic activity is unclear","No loss-of-function study of the fusion was performed","Downstream signaling pathway of the fusion was not characterized"]},{"year":2024,"claim":"Delineation of the signaling mechanism downstream of the LRP1-SNRNP25 fusion showed it physically interacts with pJNK and 37LRP to activate MMP2-dependent invasion, resolving the pathway through which the fusion drives osteosarcoma aggressiveness.","evidence":"Co-IP–mass spectrometry, epistasis experiments with JNK inhibitor SP600125 and 37LRP siRNA, Transwell/scratch assays, and in vivo xenograft validation","pmids":["38678020"],"confidence":"Medium","gaps":["The contribution of SNRNP25 exon 2 sequences versus LRP1 exon 8 sequences to signaling activation has not been dissected","No structural information on the fusion protein","Endogenous expression levels and clinical penetrance of the fusion remain limited to small patient cohorts"]},{"year":2025,"claim":"Cryo-EM structures of the human U11 snRNP revealed for the first time the precise architectural role of SNRNP25: it directly recognizes U11 snRNA and is positioned at the distal end of the particle, bridged to SNRNP48 by PDCD7, establishing its function in minor spliceosome assembly.","evidence":"Cryo-EM reconstruction of apo and substrate-bound 13-subunit human U11 snRNP","pmids":["39809272"],"confidence":"High","gaps":["The specific RNA contacts made by SNRNP25 have not been mutationally validated","Functional consequences of SNRNP25 depletion on U12-type intron splicing efficiency have not been measured in human cells","No structure of the U11/U12 di-snRNP with SNRNP25 in the context of splice site recognition"]},{"year":2025,"claim":"Genetic deletion mapping in mice identified Snrnp25 as the strongest candidate gene for peri-implantation lethality, demonstrating that minor spliceosome function is essential for the earliest stages of mammalian development.","evidence":"Molecular deletion mapping, sequence analysis, and expression profiling of the Hbab2(th) deletion spanning the Snrnp25 locus in mouse","pmids":["40399475"],"confidence":"Medium","gaps":["Lethality has not been confirmed by targeted Snrnp25 knockout or rescue experiment","Other genes within the deletion interval have not been fully excluded","The specific splicing defects underlying embryonic lethality are unknown"]},{"year":null,"claim":"It remains unknown how SNRNP25 depletion affects global U12-type intron splicing, what structural determinants of SNRNP25 are critical for U11 snRNA binding, and whether SNRNP25 has functions outside the minor spliceosome.","evidence":"","pmids":[],"confidence":"High","gaps":["No transcriptome-wide splicing analysis upon SNRNP25 loss in mammalian cells","No mutagenesis study of SNRNP25 RNA-binding residues","Potential non-spliceosomal roles unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0]}],"complexes":["U11 snRNP (minor spliceosome)"],"partners":["SNRNP48","PDCD7"],"other_free_text":[]},"mechanistic_narrative":"SNRNP25 is a structural subunit of the human U11 snRNP of the minor (U12-dependent) spliceosome, where it specifically recognizes U11 snRNA and is bridged to SNRNP48 via PDCD7 at the distal end of the particle, contributing to U12-type 5' splice site recognition [PMID:39809272]. Loss of Snrnp25 in mice causes peri-implantation lethality, indicating it is essential for early mammalian development [PMID:40399475]. A recurrent LRP1-SNRNP25 fusion gene in osteosarcoma drives cell invasion and migration through activation of the pJNK/37LRP/MMP2 signaling pathway [PMID:25300797, PMID:38678020]."},"prefetch_data":{"uniprot":{"accession":"Q9BV90","full_name":"U11/U12 small nuclear ribonucleoprotein 25 kDa protein","aliases":["Minus-99 protein"],"length_aa":132,"mass_kda":15.3,"function":"","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9BV90/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SNRNP25","classification":"Common Essential","n_dependent_lines":1202,"n_total_lines":1208,"dependency_fraction":0.9950331125827815},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SNRNP25","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytokinetic bridge","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":123.3}],"url":"https://www.proteinatlas.org/search/SNRNP25"},"hgnc":{"alias_symbol":["U11/U12-25K"],"prev_symbol":["C16orf33"]},"alphafold":{"accession":"Q9BV90","domains":[{"cath_id":"-","chopping":"1-37","consensus_level":"medium","plddt":82.6695,"start":1,"end":37},{"cath_id":"3.10.20.90","chopping":"41-132","consensus_level":"medium","plddt":93.7391,"start":41,"end":132}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BV90","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BV90-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BV90-F1-predicted_aligned_error_v6.png","plddt_mean":90.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNRNP25","jax_strain_url":"https://www.jax.org/strain/search?query=SNRNP25"},"sequence":{"accession":"Q9BV90","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BV90.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BV90/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BV90"}},"corpus_meta":[{"pmid":"16782894","id":"PMC_16782894","title":"Active chromatin hub of the mouse alpha-globin locus forms in a transcription factory of clustered housekeeping genes.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16782894","citation_count":91,"is_preprint":false},{"pmid":"26738504","id":"PMC_26738504","title":"Roles of low-density lipoprotein receptor-related protein 1 in tumors.","date":"2016","source":"Chinese journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/26738504","citation_count":53,"is_preprint":false},{"pmid":"25300797","id":"PMC_25300797","title":"Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.","date":"2014","source":"Journal of hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/25300797","citation_count":29,"is_preprint":false},{"pmid":"27091878","id":"PMC_27091878","title":"The Arabidopsis homolog of human minor spliceosomal protein U11-48K plays a crucial role in U12 intron splicing and plant development.","date":"2016","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/27091878","citation_count":20,"is_preprint":false},{"pmid":"25418192","id":"PMC_25418192","title":"Investigation of osteosarcoma genomics and its impact on targeted therapy: an international collaboration to conquer human osteosarcoma.","date":"2014","source":"Chinese journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/25418192","citation_count":10,"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":6,"is_preprint":false},{"pmid":"38678020","id":"PMC_38678020","title":"The fusion gene LRP1-SNRNP25 drives invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway in osteosarcoma.","date":"2024","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/38678020","citation_count":2,"is_preprint":false},{"pmid":"40399475","id":"PMC_40399475","title":"Snrnp25 is a candidate for the peri-implantation lethal phenotype of the Hba deletions.","date":"2025","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/40399475","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5525,"output_tokens":1105,"usd":0.016575},"stage2":{"model":"claude-opus-4-6","input_tokens":4305,"output_tokens":1476,"usd":0.087637},"total_usd":0.104212,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structures of the 13-subunit human U11 snRNP complex revealed that SNRNP25 specifically recognizes U11 snRNA and that PDCD7 bridges SNRNP25 and SNRNP48, which are located at the distal ends of the particle, establishing the architectural role of SNRNP25 within the minor spliceosome.\",\n      \"method\": \"Cryo-EM reconstruction of apo and substrate-bound human U11 snRNP complex\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure with functional validation of RNA and protein interactions in a single rigorous study\",\n      \"pmids\": [\"39809272\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SNRNP25 loss (via the Hbab2(th) deletion in mouse) is identified as the candidate gene most likely responsible for peri-implantation lethality in homozygous mice, indicating SNRNP25 is essential for early mammalian development.\",\n      \"method\": \"Molecular deletion mapping, sequence analysis, and expression analysis of Hbab2(th) mouse deletion spanning the Snrnp25 locus\",\n      \"journal\": \"Mammalian genome\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic/genomic mapping with molecular analysis, but candidate status not yet confirmed by rescue experiment\",\n      \"pmids\": [\"40399475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The LRP1-SNRNP25 fusion gene (formed by fusion of LRP1 and SNRNP25 sequences) promotes migration and invasion of SAOS-2 osteosarcoma cells, as demonstrated by overexpression experiments.\",\n      \"method\": \"Transcriptome sequencing, RT-PCR, Sanger sequencing, FISH validation, and cell migration/invasion assays with LRP1-SNRNP25 overexpression in SAOS-2 cells\",\n      \"journal\": \"Journal of hematology & oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional overexpression with multiple orthogonal validation methods, but involves a fusion protein not wild-type SNRNP25\",\n      \"pmids\": [\"25300797\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The LRP1-SNRNP25 fusion protein (LRP1 exon 8 fused to SNRNP25 exon 2) promotes osteosarcoma cell invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway; co-IP demonstrated that LRP1-SNRNP25 physically interacts with pJNK and 37LRP proteins, and 37LRP knockdown reduced MMP2 levels downstream.\",\n      \"method\": \"Whole-genome sequencing, scratch/Transwell assays, western blotting, co-immunoprecipitation-mass spectrometry, co-IP, immunofluorescence, siRNA knockdown, pJNK inhibitor (SP600125) treatment, and in vivo xenograft with immunohistochemistry\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods including co-IP, epistasis by inhibitor/siRNA, and in vivo validation; involves fusion protein context\",\n      \"pmids\": [\"38678020\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNRNP25 is a component of the human U11 snRNP of the minor spliceosome, where it specifically recognizes U11 snRNA and is bridged to SNRNP48 via PDCD7 at the distal end of the particle, contributing to U12-type 5' splice site recognition; loss of Snrnp25 in mice is associated with peri-implantation lethality, while a recurrent LRP1-SNRNP25 fusion in osteosarcoma drives cell invasion and migration through the pJNK/37LRP/MMP2 signaling pathway.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SNRNP25 is a structural subunit of the human U11 snRNP of the minor (U12-dependent) spliceosome, where it specifically recognizes U11 snRNA and is bridged to SNRNP48 via PDCD7 at the distal end of the particle, contributing to U12-type 5' splice site recognition [PMID:39809272]. Loss of Snrnp25 in mice causes peri-implantation lethality, indicating it is essential for early mammalian development [PMID:40399475]. A recurrent LRP1-SNRNP25 fusion gene in osteosarcoma drives cell invasion and migration through activation of the pJNK/37LRP/MMP2 signaling pathway [PMID:25300797, PMID:38678020].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Identification of a recurrent LRP1-SNRNP25 fusion gene in osteosarcoma established that SNRNP25 participates in oncogenic gene fusions and that the fusion product promotes tumor cell migration and invasion.\",\n      \"evidence\": \"Transcriptome sequencing, RT-PCR, FISH validation, and overexpression migration/invasion assays in SAOS-2 osteosarcoma cells\",\n      \"pmids\": [\"25300797\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism involves a fusion protein, not wild-type SNRNP25, so the contribution of SNRNP25 sequences to oncogenic activity is unclear\",\n        \"No loss-of-function study of the fusion was performed\",\n        \"Downstream signaling pathway of the fusion was not characterized\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Delineation of the signaling mechanism downstream of the LRP1-SNRNP25 fusion showed it physically interacts with pJNK and 37LRP to activate MMP2-dependent invasion, resolving the pathway through which the fusion drives osteosarcoma aggressiveness.\",\n      \"evidence\": \"Co-IP–mass spectrometry, epistasis experiments with JNK inhibitor SP600125 and 37LRP siRNA, Transwell/scratch assays, and in vivo xenograft validation\",\n      \"pmids\": [\"38678020\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The contribution of SNRNP25 exon 2 sequences versus LRP1 exon 8 sequences to signaling activation has not been dissected\",\n        \"No structural information on the fusion protein\",\n        \"Endogenous expression levels and clinical penetrance of the fusion remain limited to small patient cohorts\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Cryo-EM structures of the human U11 snRNP revealed for the first time the precise architectural role of SNRNP25: it directly recognizes U11 snRNA and is positioned at the distal end of the particle, bridged to SNRNP48 by PDCD7, establishing its function in minor spliceosome assembly.\",\n      \"evidence\": \"Cryo-EM reconstruction of apo and substrate-bound 13-subunit human U11 snRNP\",\n      \"pmids\": [\"39809272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific RNA contacts made by SNRNP25 have not been mutationally validated\",\n        \"Functional consequences of SNRNP25 depletion on U12-type intron splicing efficiency have not been measured in human cells\",\n        \"No structure of the U11/U12 di-snRNP with SNRNP25 in the context of splice site recognition\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Genetic deletion mapping in mice identified Snrnp25 as the strongest candidate gene for peri-implantation lethality, demonstrating that minor spliceosome function is essential for the earliest stages of mammalian development.\",\n      \"evidence\": \"Molecular deletion mapping, sequence analysis, and expression profiling of the Hbab2(th) deletion spanning the Snrnp25 locus in mouse\",\n      \"pmids\": [\"40399475\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Lethality has not been confirmed by targeted Snrnp25 knockout or rescue experiment\",\n        \"Other genes within the deletion interval have not been fully excluded\",\n        \"The specific splicing defects underlying embryonic lethality are unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how SNRNP25 depletion affects global U12-type intron splicing, what structural determinants of SNRNP25 are critical for U11 snRNA binding, and whether SNRNP25 has functions outside the minor spliceosome.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No transcriptome-wide splicing analysis upon SNRNP25 loss in mammalian cells\",\n        \"No mutagenesis study of SNRNP25 RNA-binding residues\",\n        \"Potential non-spliceosomal roles unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"U11 snRNP (minor spliceosome)\"],\n    \"partners\": [\"SNRNP48\", \"PDCD7\"],\n    \"other_free_text\": []\n  }\n}\n```"}