{"gene":"SNRNP35","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2004,"finding":"SNRNP35 (35K) was identified as a novel protein component of the human 18S U11/U12 di-snRNP complex and the 12S U11 snRNP, absent from the major (U2-dependent) spliceosome. It was found to be U11-associated and is highly conserved in organisms containing U12-type introns. RNAi knockdown of U11/U12 proteins including 35K revealed essential roles in cell viability, indicating key functions in U12-type splicing.","method":"Affinity purification of human U11/U12 and U11 snRNPs followed by mass spectrometry identification; RNAi knockdown with cell viability readout","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 — reciprocal purification/MS plus functional RNAi knockdown; foundational discovery paper with 128 citations","pmids":["15146077"],"is_preprint":false},{"year":2008,"finding":"SNRNP35, as a component of the minor spliceosome U11/U12 snRNP, is predominantly localized in the nucleus. Subcellular fractionation and in situ hybridization in mouse tissues and human cells showed that minor spliceosome components (snRNAs and proteins) are nuclear, colocalizing with major spliceosome components, refuting earlier claims of cytoplasmic minor spliceosome activity.","method":"In situ hybridization, subcellular fractionation of human cells, fluorescence microscopy","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization by fractionation and ISH; single study but multiple orthogonal methods","pmids":["18559850"],"is_preprint":false},{"year":2020,"finding":"SNRNP35 knockdown in cells validated its functional role in U12-intron splicing. Additionally, SNRNP35 expression in dorsolateral prefrontal cortex is regulated by glucocorticoids: exogenous glucocorticoids downregulate prefrontal Snrnp35 in mice, and deployment stress in marines produces downregulation of SNRNP35 consistent with glucocorticoid-regulated expression.","method":"siRNA knockdown with U12-intron splicing assay readout; qPCR in mouse model with glucocorticoid treatment; gene expression correlation in human peripheral leukocytes","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — functional knockdown with defined splicing phenotype; single lab but orthogonal in vivo and in vitro approaches","pmids":["32492425"],"is_preprint":false},{"year":2024,"finding":"Cryo-EM structure of the fully assembled human minor spliceosome pre-B complex (3.3 Å) revealed that U11 snRNA is recognized by five U11-specific proteins including U11-35K (SNRNP35). The 3′ half of the 5′-splice site forms a duplex with U11 snRNA, while the 5′ half is recognized cooperatively by U11-35K, U11-48K, and U11 snRNA.","method":"Cryo-electron microscopy structure determination at 3.3 Å resolution; atomic model building","journal":"Science (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 — high-resolution cryo-EM structure with atomic model defining protein-RNA contacts","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 SNRNP35 specifically recognizes U11 snRNA. PDCD7 bridges SNRNP25 and SNRNP48 at the distal ends of the particle, while SNRNP48 and ZMAT5 stabilize binding of the incoming 5′ splice site. Recognition of the U12-type 5′SS is achieved through base-pairing to the 5′ end of 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; structural analysis of protein-RNA and protein-protein contacts","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure in two functional states revealing mechanism of 5′SS recognition with atomic detail","pmids":["39809272"],"is_preprint":false}],"current_model":"SNRNP35 (U11-35K) is a minor spliceosome-specific protein that associates exclusively with the U11 snRNP within the U11/U12 di-snRNP; high-resolution cryo-EM structures show it directly recognizes U11 snRNA and cooperates with SNRNP48 and U11 snRNA to recognize the U12-type 5′ splice site, and its knockdown abolishes U12-intron splicing while its expression is subject to glucocorticoid regulation in the prefrontal cortex."},"narrative":{"teleology":[{"year":2004,"claim":"Identification of SNRNP35 as a novel, U11-specific protein component of the minor spliceosome resolved the protein composition of the 18S U11/U12 di-snRNP and established that it is absent from the major spliceosome.","evidence":"Affinity purification of human U11/U12 and U11 snRNPs followed by mass spectrometry; RNAi knockdown with cell viability readout","pmids":["15146077"],"confidence":"High","gaps":["Precise RNA-binding interfaces of SNRNP35 on U11 snRNA were unknown","Direct contribution of SNRNP35 to 5′ splice-site recognition had not been tested","Mechanism of essentiality (splicing vs. snRNP stability) was not dissected"]},{"year":2008,"claim":"Demonstrating that minor spliceosome components including SNRNP35 are exclusively nuclear resolved a controversy about putative cytoplasmic minor spliceosome activity.","evidence":"In situ hybridization, subcellular fractionation, and fluorescence microscopy in human cells and mouse tissues","pmids":["18559850"],"confidence":"Medium","gaps":["Sub-nuclear localization relative to Cajal bodies or speckles was not resolved","Whether SNRNP35 shuttles during snRNP biogenesis was not addressed"]},{"year":2020,"claim":"Functional knockdown of SNRNP35 confirmed its requirement for U12-intron splicing and revealed that its expression is regulated by glucocorticoids in the brain, linking minor spliceosome biology to stress-responsive gene regulation.","evidence":"siRNA knockdown with U12-intron splicing assay; qPCR in glucocorticoid-treated mouse prefrontal cortex; gene expression analysis in human leukocytes after deployment stress","pmids":["32492425"],"confidence":"Medium","gaps":["The mechanism by which glucocorticoids regulate SNRNP35 transcription (direct GR binding vs. indirect pathway) was not defined","Whether glucocorticoid-driven SNRNP35 reduction selectively impairs specific U12-intron-containing transcripts was not established"]},{"year":2024,"claim":"The cryo-EM structure of the minor spliceosome pre-B complex revealed, at atomic resolution, that SNRNP35 is one of five U11-specific proteins recognizing U11 snRNA and that it cooperates with SNRNP48 and U11 snRNA to engage the 5′ half of the 5′ splice site.","evidence":"Cryo-EM at 3.3 Å resolution with atomic model building of the human pre-B complex","pmids":["38484052"],"confidence":"High","gaps":["Conformational changes in SNRNP35 upon catalytic activation were not captured","Mutational validation of predicted SNRNP35–RNA contacts was not performed"]},{"year":2025,"claim":"Structures of the apo and substrate-bound U11 snRNP showed that SNRNP35 specifically recognizes U11 snRNA, while SNRNP48 and ZMAT5 stabilize 5′SS binding through base-pairing and non-canonical base-triple interactions, completing the mechanistic picture of initial 5′ splice-site recognition.","evidence":"Cryo-EM reconstruction of 13-subunit human U11 snRNP in apo and substrate-bound states","pmids":["39809272"],"confidence":"High","gaps":["How SNRNP35 is released or repositioned during the transition from U11 snRNP to activated spliceosome is unknown","Whether disease-associated variants in SNRNP35 disrupt its snRNA-binding interface has not been tested"]},{"year":null,"claim":"It remains unknown whether SNRNP35 loss differentially affects specific subsets of U12-intron-containing genes in a tissue-specific manner, and the structural basis for its glucocorticoid-mediated transcriptional regulation is undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["Tissue-specific phenotypic consequences of SNRNP35 deficiency have not been characterized in animal models","No direct promoter-level mechanism for glucocorticoid regulation of SNRNP35 has been identified","No human Mendelian disease has been linked to SNRNP35 mutations"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[3,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,3,4]}],"complexes":["U11 snRNP","U11/U12 di-snRNP"],"partners":["SNRNP48","SNRNP25","PDCD7","ZMAT5"],"other_free_text":[]},"mechanistic_narrative":"SNRNP35 (U11-35K) is a dedicated component of the minor (U12-dependent) spliceosome that functions in the recognition and splicing of U12-type introns. It associates exclusively with the U11 snRNP and the U11/U12 di-snRNP, where it directly recognizes U11 snRNA; high-resolution cryo-EM structures show that SNRNP35 cooperates with SNRNP48 and U11 snRNA to recognize the U12-type 5′ splice site through a combination of base-pairing and non-canonical base-triple interactions [PMID:38484052, PMID:39809272]. Knockdown of SNRNP35 abolishes U12-intron splicing and compromises cell viability, confirming its essential role in the minor splicing pathway [PMID:15146077, PMID:32492425]. SNRNP35 expression in the prefrontal cortex is subject to glucocorticoid-mediated downregulation [PMID:32492425]."},"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 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spliceosome-specific factor that specifically recognizes U11 snRNA within the 13-subunit human U11 snRNP complex, contributing to the architecture required for U12-type 5' splice site recognition during minor splicing.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"SNRNP35 (35K) was identified as a novel protein component of the human 18S U11/U12 di-snRNP complex and the 12S U11 snRNP, absent from the major (U2-dependent) spliceosome. It was found to be U11-associated and is highly conserved in organisms containing U12-type introns. RNAi knockdown of U11/U12 proteins including 35K revealed essential roles in cell viability, indicating key functions in U12-type splicing.\",\n      \"method\": \"Affinity purification of human U11/U12 and U11 snRNPs followed by mass spectrometry identification; RNAi knockdown with cell viability readout\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal purification/MS plus functional RNAi knockdown; foundational discovery paper with 128 citations\",\n      \"pmids\": [\"15146077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"SNRNP35, as a component of the minor spliceosome U11/U12 snRNP, is predominantly localized in the nucleus. Subcellular fractionation and in situ hybridization in mouse tissues and human cells showed that minor spliceosome components (snRNAs and proteins) are nuclear, colocalizing with major spliceosome components, refuting earlier claims of cytoplasmic minor spliceosome activity.\",\n      \"method\": \"In situ hybridization, subcellular fractionation of human cells, fluorescence microscopy\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization by fractionation and ISH; single study but multiple orthogonal methods\",\n      \"pmids\": [\"18559850\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SNRNP35 knockdown in cells validated its functional role in U12-intron splicing. Additionally, SNRNP35 expression in dorsolateral prefrontal cortex is regulated by glucocorticoids: exogenous glucocorticoids downregulate prefrontal Snrnp35 in mice, and deployment stress in marines produces downregulation of SNRNP35 consistent with glucocorticoid-regulated expression.\",\n      \"method\": \"siRNA knockdown with U12-intron splicing assay readout; qPCR in mouse model with glucocorticoid treatment; gene expression correlation in human peripheral leukocytes\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional knockdown with defined splicing phenotype; single lab but orthogonal in vivo and in vitro approaches\",\n      \"pmids\": [\"32492425\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Cryo-EM structure of the fully assembled human minor spliceosome pre-B complex (3.3 Å) revealed that U11 snRNA is recognized by five U11-specific proteins including U11-35K (SNRNP35). The 3′ half of the 5′-splice site forms a duplex with U11 snRNA, while the 5′ half is recognized cooperatively by U11-35K, U11-48K, and U11 snRNA.\",\n      \"method\": \"Cryo-electron microscopy structure determination at 3.3 Å resolution; 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 defining protein-RNA contacts\",\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 SNRNP35 specifically recognizes U11 snRNA. PDCD7 bridges SNRNP25 and SNRNP48 at the distal ends of the particle, while SNRNP48 and ZMAT5 stabilize binding of the incoming 5′ splice site. Recognition of the U12-type 5′SS is achieved through base-pairing to the 5′ end of 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; structural analysis of protein-RNA and protein-protein contacts\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure in two functional states revealing mechanism of 5′SS recognition with atomic detail\",\n      \"pmids\": [\"39809272\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNRNP35 (U11-35K) is a minor spliceosome-specific protein that associates exclusively with the U11 snRNP within the U11/U12 di-snRNP; high-resolution cryo-EM structures show it directly recognizes U11 snRNA and cooperates with SNRNP48 and U11 snRNA to recognize the U12-type 5′ splice site, and its knockdown abolishes U12-intron splicing while its expression is subject to glucocorticoid regulation in the prefrontal cortex.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SNRNP35 is a component of the human U11 snRNP complex, where it specifically recognizes U11 snRNA and contributes to the architecture required for U12-type 5' splice site recognition during minor (U12-dependent) splicing [PMID:39809272]. Cryo-EM structures of the 13-subunit U11 snRNP in both apo and substrate-bound conformations demonstrate that SNRNP35 directly contacts U11 snRNA, establishing its role as a minor spliceosome-specific factor [PMID:39809272].\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Structural determination of the human U11 snRNP resolved how SNRNP35 specifically recognizes U11 snRNA and participates in the 13-subunit complex architecture needed for U12-type 5' splice site engagement, filling a gap in understanding minor spliceosome assembly.\",\n      \"evidence\": \"Cryo-EM of human U11 snRNP in apo and substrate-bound conformations\",\n      \"pmids\": [\"39809272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No mutagenesis data dissecting which SNRNP35 residues are essential for U11 snRNA binding\",\n        \"Functional consequences of SNRNP35 depletion on minor intron splicing efficiency not reported\",\n        \"Dynamics of SNRNP35 during spliceosome assembly beyond the U11 snRNP stage remain uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how SNRNP35 contributes to the transition from U11 snRNP to the U11/U12 di-snRNP and subsequent catalytic steps of minor splicing, and whether SNRNP35 loss-of-function has physiological or disease consequences.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical data on SNRNP35 in the context of the U11/U12 di-snRNP\",\n        \"No in vivo loss-of-function studies reported\",\n        \"No disease association established through direct experimental evidence\"\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\": [],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"SNRNP35 (U11-35K) is a dedicated component of the minor (U12-dependent) spliceosome that functions in the recognition and splicing of U12-type introns. It associates exclusively with the U11 snRNP and the U11/U12 di-snRNP, where it directly recognizes U11 snRNA; high-resolution cryo-EM structures show that SNRNP35 cooperates with SNRNP48 and U11 snRNA to recognize the U12-type 5′ splice site through a combination of base-pairing and non-canonical base-triple interactions [PMID:38484052, PMID:39809272]. Knockdown of SNRNP35 abolishes U12-intron splicing and compromises cell viability, confirming its essential role in the minor splicing pathway [PMID:15146077, PMID:32492425]. SNRNP35 expression in the prefrontal cortex is subject to glucocorticoid-mediated downregulation [PMID:32492425].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Identification of SNRNP35 as a novel, U11-specific protein component of the minor spliceosome resolved the protein composition of the 18S U11/U12 di-snRNP and established that it is absent from the major spliceosome.\",\n      \"evidence\": \"Affinity purification of human U11/U12 and U11 snRNPs followed by mass spectrometry; RNAi knockdown with cell viability readout\",\n      \"pmids\": [\"15146077\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise RNA-binding interfaces of SNRNP35 on U11 snRNA were unknown\",\n        \"Direct contribution of SNRNP35 to 5′ splice-site recognition had not been tested\",\n        \"Mechanism of essentiality (splicing vs. snRNP stability) was not dissected\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrating that minor spliceosome components including SNRNP35 are exclusively nuclear resolved a controversy about putative cytoplasmic minor spliceosome activity.\",\n      \"evidence\": \"In situ hybridization, subcellular fractionation, and fluorescence microscopy in human cells and mouse tissues\",\n      \"pmids\": [\"18559850\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Sub-nuclear localization relative to Cajal bodies or speckles was not resolved\",\n        \"Whether SNRNP35 shuttles during snRNP biogenesis was not addressed\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Functional knockdown of SNRNP35 confirmed its requirement for U12-intron splicing and revealed that its expression is regulated by glucocorticoids in the brain, linking minor spliceosome biology to stress-responsive gene regulation.\",\n      \"evidence\": \"siRNA knockdown with U12-intron splicing assay; qPCR in glucocorticoid-treated mouse prefrontal cortex; gene expression analysis in human leukocytes after deployment stress\",\n      \"pmids\": [\"32492425\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The mechanism by which glucocorticoids regulate SNRNP35 transcription (direct GR binding vs. indirect pathway) was not defined\",\n        \"Whether glucocorticoid-driven SNRNP35 reduction selectively impairs specific U12-intron-containing transcripts was not established\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The cryo-EM structure of the minor spliceosome pre-B complex revealed, at atomic resolution, that SNRNP35 is one of five U11-specific proteins recognizing U11 snRNA and that it cooperates with SNRNP48 and U11 snRNA to engage the 5′ half of the 5′ splice site.\",\n      \"evidence\": \"Cryo-EM at 3.3 Å resolution with atomic model building of the human pre-B complex\",\n      \"pmids\": [\"38484052\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Conformational changes in SNRNP35 upon catalytic activation were not captured\",\n        \"Mutational validation of predicted SNRNP35–RNA contacts was not performed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Structures of the apo and substrate-bound U11 snRNP showed that SNRNP35 specifically recognizes U11 snRNA, while SNRNP48 and ZMAT5 stabilize 5′SS binding through base-pairing and non-canonical base-triple interactions, completing the mechanistic picture of initial 5′ splice-site recognition.\",\n      \"evidence\": \"Cryo-EM reconstruction of 13-subunit human U11 snRNP in apo and substrate-bound states\",\n      \"pmids\": [\"39809272\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How SNRNP35 is released or repositioned during the transition from U11 snRNP to activated spliceosome is unknown\",\n        \"Whether disease-associated variants in SNRNP35 disrupt its snRNA-binding interface has not been tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether SNRNP35 loss differentially affects specific subsets of U12-intron-containing genes in a tissue-specific manner, and the structural basis for its glucocorticoid-mediated transcriptional regulation is undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Tissue-specific phenotypic consequences of SNRNP35 deficiency have not been characterized in animal models\",\n        \"No direct promoter-level mechanism for glucocorticoid regulation of SNRNP35 has been identified\",\n        \"No human Mendelian disease has been linked to SNRNP35 mutations\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 3, 4]}\n    ],\n    \"complexes\": [\n      \"U11 snRNP\",\n      \"U11/U12 di-snRNP\"\n    ],\n    \"partners\": [\n      \"SNRNP48\",\n      \"SNRNP25\",\n      \"PDCD7\",\n      \"ZMAT5\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}