{"gene":"RBM27","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2020,"finding":"RBM27 (along with RBM26 and ZC3H3) is required for PAXT-mediated nuclear RNA decay. ZC3H3 interacts directly with the MTR4-ZFC3H1 core dimer of the PAXT connection, and loss of RBM27 results in accumulation of PAXT substrates (nuclear polyadenylated RNA). RBM27 was identified as a component of MTR4-ZFC3H1-containing complexes under conditions favoring PAXT assembly.","method":"Nuclear pA+-RNA bound proteome characterization, MTR4-ZFC3H1 complex immunoprecipitation/MS, knockdown with PAXT substrate accumulation readout","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP/MS identifying complex membership, loss-of-function with defined substrate accumulation phenotype, multiple orthogonal methods in a single focused study","pmids":["31950173"],"is_preprint":false},{"year":2005,"finding":"The mouse Psc1 protein (ARRS1/RBM27 ortholog) contains an RS domain and an RNA recognition motif (RRM) in a novel sequential arrangement defining the 'acidic rich RS (ARRS)' protein family. Psc1 localizes to nuclear speckles (including speckles proximal to the nuclear periphery) and to cytoplasmic punctate structures termed 'cytospeckles'. Integration into cytospeckles is dependent on the RRM domain. Cytospeckles are dynamic and appear to traffic into the nucleus.","method":"Sequence analysis, fluorescence microscopy/live imaging of subcellular localization, domain-deletion analysis of cytospeckle targeting","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by imaging with functional domain mapping (RRM dependence), single lab with multiple methods","pmids":["15741184"],"is_preprint":false},{"year":2023,"finding":"PABPN1 recruits RBM26 and RBM27 to promote splicing of last introns with weak 3' splice sites. This interaction is mediated through the coiled-coil and RRM domain of RBM27. Tethering PABPN1 to non-polyadenylated transcripts also promotes splicing, indicating a direct role. PABPN1 depletion induces retention of a group of introns that show strong 3'-end bias.","method":"TurboID-MS interactome, PABPN1 depletion with splicing readout, domain interaction mapping (coiled-coil and RRM of RBM27), tethering assay","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-based interactome with domain-level functional validation, single lab with multiple orthogonal methods","pmids":["37661812"],"is_preprint":false},{"year":2023,"finding":"RBM27 is recruited to transcription start sites (TSSs) of hundreds of genes as part of the PAXT complex. Genome-wide ChIP/binding mapping shows RBM27 co-occupies TSSs with ZFC3H1 and PAPγ. Loss of ZFC3H1 abolishes recruitment of RBM27 (and other PAXT subunits including PAPγ) to TSSs and concomitantly increases PROMPT ncRNA abundance at the same sites.","method":"Genome-wide binding site mapping (ChIP or equivalent), proteomic analysis identifying additional PAXT subunits, ZFC3H1 loss-of-function with PROMPT accumulation readout","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide binding data combined with loss-of-function epistasis, single lab study","pmids":["37875486"],"is_preprint":false},{"year":2024,"finding":"RBM-26, the C. elegans ortholog of RBM27, protects against axon degeneration by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor in neurons. The mRNA encoding MALS-1 was identified as a direct binding partner of RBM-26 by biochemical screen. Loss of RBM-26 causes dramatic overexpression of mals-1 mRNA and MALS-1 protein. Genetic analysis (double mutant epistasis) showed that overexpression of MALS-1 is responsible for the mitochondrial dysfunction and axon degeneration defects in rbm-26 mutants. Autism-associated missense variants in RBM-26 cause decreased RBM-26 protein expression and the same axonal defects.","method":"Biochemical mRNA-binding screen, loss-of-function genetics (rbm-26 null mutants), genetic epistasis (rbm-26; mals-1 double mutants), live imaging of axon morphology, autism-variant missense allele analysis","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — RNA-binding biochemistry, genetic epistasis, and disease variant functional validation in multiple orthogonal approaches in a single focused study; preprint and peer-reviewed versions converge","pmids":["39480871"],"is_preprint":false},{"year":2024,"finding":"RBM-26 (RBM27 ortholog in C. elegans) directly binds the mals-1 (MALSU1) mRNA to negatively regulate its expression, and this mechanism protects against mitochondrial dysfunction and axon degeneration during neurodevelopment. (Preprint version of the above peer-reviewed finding.)","method":"Biochemical mRNA-binding screen, genetic loss-of-function, epistasis analysis","journal":"bioRxiv","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — same study as peer-reviewed PMID:39480871; preprint confirms findings; multiple orthogonal methods","pmids":["37873356"],"is_preprint":true}],"current_model":"RBM27 is a nuclear RNA-binding protein (containing an RRM and RS/ARRS domain) that functions as a component of the PAXT complex, where it is recruited to transcription start sites via ZFC3H1 and contributes to nuclear polyadenylated RNA turnover; it also interacts with PABPN1 through its coiled-coil and RRM domains to promote splicing of last introns with weak 3' splice sites; and its C. elegans ortholog (RBM-26) directly binds MALSU1 (MALS-1) mRNA to suppress its expression, thereby protecting against mitochondrial dysfunction and axon degeneration during neurodevelopment."},"narrative":{"mechanistic_narrative":"RBM27 is a nuclear RNA-binding protein, defined by an RRM and an acidic-rich RS (ARRS) domain, that operates at the interface of nuclear RNA surveillance and mRNA processing [PMID:15741184]. It functions as a component of the PAXT connection: under conditions favoring PAXT assembly it associates with the MTR4-ZFC3H1 core, and its loss causes accumulation of nuclear polyadenylated PAXT substrates, establishing a role in nuclear polyadenylated RNA turnover [PMID:31950173]. RBM27 is recruited to transcription start sites of hundreds of genes together with ZFC3H1 and PAPγ, and this recruitment depends entirely on ZFC3H1, whose loss both displaces RBM27 from TSSs and increases PROMPT non-coding RNA abundance at those sites [PMID:37875486]. In a distinct processing role, PABPN1 recruits RBM27 through its coiled-coil and RRM domains to promote splicing of last introns bearing weak 3' splice sites [PMID:37661812]. The C. elegans ortholog RBM-26 directly binds the mRNA encoding the mitoribosomal assembly factor MALS-1 (MALSU1) to suppress its expression, thereby protecting neurons against mitochondrial dysfunction and axon degeneration; autism-associated missense variants reduce RBM-26 protein and reproduce these axonal defects [PMID:39480871].","teleology":[{"year":2005,"claim":"Before functional assignment, the domain architecture and subcellular behavior of the RBM27 ortholog were unknown; this work defined it as an RRM/RS-domain protein of a novel ARRS family with dynamic nuclear-speckle and cytoplasmic localization.","evidence":"Sequence analysis plus fluorescence/live imaging and domain-deletion mapping of the mouse Psc1 ortholog","pmids":["15741184"],"confidence":"Medium","gaps":["No RNA target or biochemical activity assigned","Functional significance of cytospeckle trafficking unresolved","Human ortholog not directly tested"]},{"year":2020,"claim":"It was unknown whether RBM27 participates in nuclear RNA decay; this study placed it within MTR4-ZFC3H1 (PAXT) complexes and showed its loss causes accumulation of nuclear polyadenylated PAXT substrates.","evidence":"Nuclear pA+-RNA proteome, MTR4-ZFC3H1 co-IP/MS, and knockdown with substrate-accumulation readout","pmids":["31950173"],"confidence":"High","gaps":["Whether RBM27 contacts RNA directly within PAXT not resolved","Mechanism of RBM27 integration into the complex undefined"]},{"year":2023,"claim":"How RBM27 reaches PAXT target loci and what processing role it has beyond decay were open; these studies showed ZFC3H1-dependent recruitment to TSSs controlling PROMPT levels, and a PABPN1-dependent role in splicing weak-3'-splice-site terminal introns.","evidence":"Genome-wide binding mapping with ZFC3H1 loss-of-function (PROMPT readout); TurboID interactome, PABPN1 depletion splicing assays, domain mapping, and tethering","pmids":["37875486","37661812"],"confidence":"Medium","gaps":["Direct RNA-binding specificity of RBM27 not defined","Relationship between TSS recruitment and splicing role unintegrated","Structural basis of PABPN1-RBM27 coiled-coil/RRM interaction unknown"]},{"year":2024,"claim":"Whether RBM27 has a direct mRNA target with physiological consequence was unknown; the C. elegans ortholog was shown to directly bind mals-1 (MALSU1) mRNA to repress it, with epistasis proving MALS-1 overexpression drives the mitochondrial and axon-degeneration defects, and autism variants reproducing the phenotype.","evidence":"Biochemical mRNA-binding screen, rbm-26 null genetics, rbm-26;mals-1 epistasis, axon imaging, and autism missense allele analysis (peer-reviewed and preprint)","pmids":["39480871","37873356"],"confidence":"High","gaps":["Whether human RBM27 represses MALSU1 mRNA not tested","Connection between PAXT/splicing roles and this single-target repression unclear","Molecular basis of how variants lower protein level unresolved"]},{"year":null,"claim":"How RBM27's nuclear RNA-decay, terminal-intron splicing, and target-specific mRNA repression activities are mechanistically unified, and whether the conserved ortholog functions are shared in human neurons, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated model linking PAXT, splicing, and direct mRNA repression","No structural data on RBM27 complexes","Direct RNA-binding specificity of human RBM27 undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,1,2,4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,3]}],"complexes":["PAXT"],"partners":["ZFC3H1","MTR4","ZC3H3","PABPN1","RBM26"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9P2N5","full_name":"RNA-binding protein 27","aliases":["RNA-binding motif protein 27"],"length_aa":1060,"mass_kda":118.7,"function":"May be involved in the turnover of nuclear polyadenylated (pA+) RNA","subcellular_location":"Cytoplasm; Nucleus speckle","url":"https://www.uniprot.org/uniprotkb/Q9P2N5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RBM27","classification":"Not Classified","n_dependent_lines":110,"n_total_lines":1208,"dependency_fraction":0.09105960264900662},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TNPO3","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/search/RBM27","total_profiled":1310},"omim":[{"mim_id":"620082","title":"RNA-BINDING MOTIF PROTEIN 27; RBM27","url":"https://www.omim.org/entry/620082"},{"mim_id":"620081","title":"RNA-BINDING MOTIF PROTEIN 26; RBM26","url":"https://www.omim.org/entry/620081"},{"mim_id":"618640","title":"ZINC FINGER CCCH DOMAIN-CONTAINING PROTEIN 3; ZC3H3","url":"https://www.omim.org/entry/618640"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear speckles","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RBM27"},"hgnc":{"alias_symbol":["KIAA1311","ARRS1","Psc1","ZC3H20"],"prev_symbol":[]},"alphafold":{"accession":"Q9P2N5","domains":[{"cath_id":"3.30.70.330","chopping":"602-672","consensus_level":"high","plddt":90.781,"start":602,"end":672},{"cath_id":"1.10.150","chopping":"7-75","consensus_level":"high","plddt":85.7917,"start":7,"end":75},{"cath_id":"1.10.287","chopping":"816-887","consensus_level":"medium","plddt":86.2936,"start":816,"end":887},{"cath_id":"1.10.287","chopping":"894-939","consensus_level":"medium","plddt":83.7522,"start":894,"end":939}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2N5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2N5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2N5-F1-predicted_aligned_error_v6.png","plddt_mean":54.91},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RBM27","jax_strain_url":"https://www.jax.org/strain/search?query=RBM27"},"sequence":{"accession":"Q9P2N5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9P2N5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9P2N5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2N5"}},"corpus_meta":[{"pmid":"27302169","id":"PMC_27302169","title":"Integrated 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ZC3H3 interacts directly with the MTR4-ZFC3H1 core dimer of the PAXT connection, and loss of RBM27 results in accumulation of PAXT substrates (nuclear polyadenylated RNA). RBM27 was identified as a component of MTR4-ZFC3H1-containing complexes under conditions favoring PAXT assembly.\",\n      \"method\": \"Nuclear pA+-RNA bound proteome characterization, MTR4-ZFC3H1 complex immunoprecipitation/MS, knockdown with PAXT substrate accumulation readout\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP/MS identifying complex membership, loss-of-function with defined substrate accumulation phenotype, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"31950173\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The mouse Psc1 protein (ARRS1/RBM27 ortholog) contains an RS domain and an RNA recognition motif (RRM) in a novel sequential arrangement defining the 'acidic rich RS (ARRS)' protein family. Psc1 localizes to nuclear speckles (including speckles proximal to the nuclear periphery) and to cytoplasmic punctate structures termed 'cytospeckles'. Integration into cytospeckles is dependent on the RRM domain. Cytospeckles are dynamic and appear to traffic into the nucleus.\",\n      \"method\": \"Sequence analysis, fluorescence microscopy/live imaging of subcellular localization, domain-deletion analysis of cytospeckle targeting\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by imaging with functional domain mapping (RRM dependence), single lab with multiple methods\",\n      \"pmids\": [\"15741184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PABPN1 recruits RBM26 and RBM27 to promote splicing of last introns with weak 3' splice sites. This interaction is mediated through the coiled-coil and RRM domain of RBM27. Tethering PABPN1 to non-polyadenylated transcripts also promotes splicing, indicating a direct role. PABPN1 depletion induces retention of a group of introns that show strong 3'-end bias.\",\n      \"method\": \"TurboID-MS interactome, PABPN1 depletion with splicing readout, domain interaction mapping (coiled-coil and RRM of RBM27), tethering assay\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-based interactome with domain-level functional validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"37661812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBM27 is recruited to transcription start sites (TSSs) of hundreds of genes as part of the PAXT complex. Genome-wide ChIP/binding mapping shows RBM27 co-occupies TSSs with ZFC3H1 and PAPγ. Loss of ZFC3H1 abolishes recruitment of RBM27 (and other PAXT subunits including PAPγ) to TSSs and concomitantly increases PROMPT ncRNA abundance at the same sites.\",\n      \"method\": \"Genome-wide binding site mapping (ChIP or equivalent), proteomic analysis identifying additional PAXT subunits, ZFC3H1 loss-of-function with PROMPT accumulation readout\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide binding data combined with loss-of-function epistasis, single lab study\",\n      \"pmids\": [\"37875486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBM-26, the C. elegans ortholog of RBM27, protects against axon degeneration by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor in neurons. The mRNA encoding MALS-1 was identified as a direct binding partner of RBM-26 by biochemical screen. Loss of RBM-26 causes dramatic overexpression of mals-1 mRNA and MALS-1 protein. Genetic analysis (double mutant epistasis) showed that overexpression of MALS-1 is responsible for the mitochondrial dysfunction and axon degeneration defects in rbm-26 mutants. Autism-associated missense variants in RBM-26 cause decreased RBM-26 protein expression and the same axonal defects.\",\n      \"method\": \"Biochemical mRNA-binding screen, loss-of-function genetics (rbm-26 null mutants), genetic epistasis (rbm-26; mals-1 double mutants), live imaging of axon morphology, autism-variant missense allele analysis\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — RNA-binding biochemistry, genetic epistasis, and disease variant functional validation in multiple orthogonal approaches in a single focused study; preprint and peer-reviewed versions converge\",\n      \"pmids\": [\"39480871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBM-26 (RBM27 ortholog in C. elegans) directly binds the mals-1 (MALSU1) mRNA to negatively regulate its expression, and this mechanism protects against mitochondrial dysfunction and axon degeneration during neurodevelopment. (Preprint version of the above peer-reviewed finding.)\",\n      \"method\": \"Biochemical mRNA-binding screen, genetic loss-of-function, epistasis analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — same study as peer-reviewed PMID:39480871; preprint confirms findings; multiple orthogonal methods\",\n      \"pmids\": [\"37873356\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"RBM27 is a nuclear RNA-binding protein (containing an RRM and RS/ARRS domain) that functions as a component of the PAXT complex, where it is recruited to transcription start sites via ZFC3H1 and contributes to nuclear polyadenylated RNA turnover; it also interacts with PABPN1 through its coiled-coil and RRM domains to promote splicing of last introns with weak 3' splice sites; and its C. elegans ortholog (RBM-26) directly binds MALSU1 (MALS-1) mRNA to suppress its expression, thereby protecting against mitochondrial dysfunction and axon degeneration during neurodevelopment.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RBM27 is a nuclear RNA-binding protein, defined by an RRM and an acidic-rich RS (ARRS) domain, that operates at the interface of nuclear RNA surveillance and mRNA processing [#1]. It functions as a component of the PAXT connection: under conditions favoring PAXT assembly it associates with the MTR4-ZFC3H1 core, and its loss causes accumulation of nuclear polyadenylated PAXT substrates, establishing a role in nuclear polyadenylated RNA turnover [#0]. RBM27 is recruited to transcription start sites of hundreds of genes together with ZFC3H1 and PAPγ, and this recruitment depends entirely on ZFC3H1, whose loss both displaces RBM27 from TSSs and increases PROMPT non-coding RNA abundance at those sites [#3]. In a distinct processing role, PABPN1 recruits RBM27 through its coiled-coil and RRM domains to promote splicing of last introns bearing weak 3' splice sites [#2]. The C. elegans ortholog RBM-26 directly binds the mRNA encoding the mitoribosomal assembly factor MALS-1 (MALSU1) to suppress its expression, thereby protecting neurons against mitochondrial dysfunction and axon degeneration; autism-associated missense variants reduce RBM-26 protein and reproduce these axonal defects [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Before functional assignment, the domain architecture and subcellular behavior of the RBM27 ortholog were unknown; this work defined it as an RRM/RS-domain protein of a novel ARRS family with dynamic nuclear-speckle and cytoplasmic localization.\",\n      \"evidence\": \"Sequence analysis plus fluorescence/live imaging and domain-deletion mapping of the mouse Psc1 ortholog\",\n      \"pmids\": [\"15741184\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RNA target or biochemical activity assigned\",\n        \"Functional significance of cytospeckle trafficking unresolved\",\n        \"Human ortholog not directly tested\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"It was unknown whether RBM27 participates in nuclear RNA decay; this study placed it within MTR4-ZFC3H1 (PAXT) complexes and showed its loss causes accumulation of nuclear polyadenylated PAXT substrates.\",\n      \"evidence\": \"Nuclear pA+-RNA proteome, MTR4-ZFC3H1 co-IP/MS, and knockdown with substrate-accumulation readout\",\n      \"pmids\": [\"31950173\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether RBM27 contacts RNA directly within PAXT not resolved\",\n        \"Mechanism of RBM27 integration into the complex undefined\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"How RBM27 reaches PAXT target loci and what processing role it has beyond decay were open; these studies showed ZFC3H1-dependent recruitment to TSSs controlling PROMPT levels, and a PABPN1-dependent role in splicing weak-3'-splice-site terminal introns.\",\n      \"evidence\": \"Genome-wide binding mapping with ZFC3H1 loss-of-function (PROMPT readout); TurboID interactome, PABPN1 depletion splicing assays, domain mapping, and tethering\",\n      \"pmids\": [\"37875486\", \"37661812\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct RNA-binding specificity of RBM27 not defined\",\n        \"Relationship between TSS recruitment and splicing role unintegrated\",\n        \"Structural basis of PABPN1-RBM27 coiled-coil/RRM interaction unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether RBM27 has a direct mRNA target with physiological consequence was unknown; the C. elegans ortholog was shown to directly bind mals-1 (MALSU1) mRNA to repress it, with epistasis proving MALS-1 overexpression drives the mitochondrial and axon-degeneration defects, and autism variants reproducing the phenotype.\",\n      \"evidence\": \"Biochemical mRNA-binding screen, rbm-26 null genetics, rbm-26;mals-1 epistasis, axon imaging, and autism missense allele analysis (peer-reviewed and preprint)\",\n      \"pmids\": [\"39480871\", \"37873356\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether human RBM27 represses MALSU1 mRNA not tested\",\n        \"Connection between PAXT/splicing roles and this single-target repression unclear\",\n        \"Molecular basis of how variants lower protein level unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RBM27's nuclear RNA-decay, terminal-intron splicing, and target-specific mRNA repression activities are mechanistically unified, and whether the conserved ortholog functions are shared in human neurons, remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No integrated model linking PAXT, splicing, and direct mRNA repression\",\n        \"No structural data on RBM27 complexes\",\n        \"Direct RNA-binding specificity of human RBM27 undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 2, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [\"PAXT\"],\n    \"partners\": [\"ZFC3H1\", \"MTR4\", \"ZC3H3\", \"PABPN1\", \"RBM26\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}