{"gene":"RBM26","run_date":"2026-04-28T19:45:45","timeline":{"discoveries":[{"year":2020,"finding":"RBM26 and its paralog RBM27 are components of the PAXT (Poly(A) Tail eXosome Targeting) connection required for nuclear polyadenylated RNA decay. Loss of RBM26 leads to accumulation of PAXT substrates, establishing RBM26 as a limiting factor for PAXT-mediated RNA turnover. RBM26 was identified by characterizing nuclear pA+-RNA bound proteomes and MTR4-ZFC3H1-containing complexes.","method":"Nuclear pA+-RNA bound proteome characterization, MTR4-ZFC3H1 complex purification under PAXT-assembly-favoring conditions, siRNA knockdown with PAXT substrate accumulation assay","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 — reciprocal complex purification, loss-of-function with defined substrate accumulation phenotype, replicated with multiple orthogonal methods in single study","pmids":["31950173"],"is_preprint":false},{"year":2024,"finding":"ZFC3H1 is co-transcriptionally loaded onto RNA precursors in a 'closed' conformation that blocks exosome recruitment. For short RNAs with fewer exons, transient PAXT components ZC3H3 and RBM26/27 are preferentially recruited to the 3' end, triggering ZFC3H1 'opening' and subsequent exosomal degradation. This decoupled loading and activation mechanism routes short nuclear RNAs to degradation while longer RNAs with more exons are directed to nuclear export.","method":"Co-immunoprecipitation, RNA-seq, knockdown experiments, domain mutant analysis, nascent RNA association assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods establishing pathway position of RBM26/27 in ZFC3H1 activation mechanism","pmids":["39461342"],"is_preprint":false},{"year":2023,"finding":"PABPN1 recruits RBM26 and RBM27 to promote splicing of last introns with weak 3' splice sites. PABPN1 interacts with the coiled-coil and RRM domain of RBM27 (and by extension RBM26) to facilitate this recruitment. This function was identified via TurboID-MS interactome analysis of PABPN1 and validated functionally.","method":"TurboID proximity labeling mass spectrometry, co-immunoprecipitation, siRNA knockdown, splicing assays in HeLa cells","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 — proximity labeling MS plus co-IP and functional splicing assay, but RBM26 finding is partly inferred from RBM27 interaction domain mapping","pmids":["37661812"],"is_preprint":false},{"year":2024,"finding":"The C. elegans ortholog RBM-26 (ortholog of human RBM26/27) protects against axon degeneration during neurodevelopment by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor. Loss of RBM-26 causes dramatic overexpression of mals-1 mRNA and MALS-1 protein, and genetic analysis demonstrates that this MALS-1 overexpression is responsible for mitochondrial dysfunction and axon degeneration defects. A biochemical screen identified mals-1 mRNA as a direct binding partner of RBM-26.","method":"C. elegans genetics (loss-of-function mutants, epistasis analysis), biochemical RNA-binding screen, immunofluorescence, axon morphology assays","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis with double mutant rescue, direct mRNA binding identification, and defined axon degeneration phenotype; ortholog with consistent RNA-binding protein function","pmids":["39480871"],"is_preprint":false},{"year":2025,"finding":"In fission yeast Schizosaccharomyces japonicus, the RBM26/27 ortholog Rmn1 interacts with Pab2/PABPN1 and is essential for constitutive heterochromatin formation at centromeres. Rmn1 can interact with the histone H3 Lys9 methyltransferase Clr4, and deletion of the Pab2 N-terminal region (which disrupts its interaction with Rmn1 and ZC3H3 ortholog Red5) largely abolishes Pab2 function in heterochromatin assembly.","method":"Genetic deletion analysis, co-immunoprecipitation, ChIP (histone methylation at centromeres), epistasis in fission yeast","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 — co-IP and ChIP in ortholog system with deletion phenotype, but findings are in distantly related yeast ortholog","pmids":["40163528"],"is_preprint":false},{"year":2017,"finding":"RBM26 was identified in EBV-transformed B cells as a protein containing mono-methylated arginine (MMA) residues within RG-repeat sequences, co-immunoprecipitated using a monoclonal antibody specific for MMA-modified RG repeats and confirmed by Western blot. This places RBM26 among cellular proteins whose RG repeats serve as arginine methylation substrates.","method":"Immunoprecipitation with MMA-specific monoclonal antibody, mass spectrometry, Western blot confirmation","journal":"The Journal of general virology","confidence":"Low","confidence_rationale":"Tier 3 — single IP/MS identification with Western blot confirmation; no functional follow-up of RBM26 methylation","pmids":["28758620"],"is_preprint":false},{"year":2012,"finding":"RBM26 was identified as an mRNA-binding protein (RBP) in human HeLa cells through UV crosslinking and oligo(dT) purification (interactome capture), establishing it as a bona fide component of the human mRNA-bound proteome.","method":"UV crosslinking, oligo(dT) purification, quantitative mass spectrometry (interactome capture)","journal":"Cell","confidence":"Low","confidence_rationale":"Tier 3 — large-scale proteomics identification without functional follow-up specific to RBM26","pmids":["22658674"],"is_preprint":false},{"year":2018,"finding":"BioID proximity labeling of mRNA biology proteins placed RBM26 in the spatial organization of nuclear RNA regulatory structures, with proximity interactions connecting it to mRNA-associated processes.","method":"BioID proximity-dependent biotinylation, mass spectrometry","journal":"Molecular cell","confidence":"Low","confidence_rationale":"Tier 3 — proximity labeling without functional validation specific to RBM26","pmids":["29395067"],"is_preprint":false}],"current_model":"RBM26 is an RNA-binding protein that functions as a limiting component of the PAXT (Poly(A) Tail eXosome Targeting) connection, where it is recruited to the 3' ends of short nuclear polyadenylated RNAs to trigger ZFC3H1 'opening' and exosome-mediated degradation; additionally, it is recruited by PABPN1 to promote splicing of terminal introns with weak 3' splice sites, contains arginine-methylated RG-repeat motifs, and its C. elegans ortholog directly binds mals-1 mRNA to negatively regulate mitoribosomal assembly factor expression and protect against axon degeneration."},"narrative":{"teleology":[{"year":2012,"claim":"Establishing RBM26 as a bona fide mRNA-binding protein resolved whether its predicted RNA-binding domains were functional in vivo.","evidence":"UV crosslinking and oligo(dT) interactome capture in HeLa cells identified RBM26 in the mRNA-bound proteome","pmids":["22658674"],"confidence":"Low","gaps":["Large-scale proteomics hit without functional follow-up specific to RBM26","RNA targets and binding specificity unknown","No mechanistic context for RBM26 function"]},{"year":2017,"claim":"Detection of mono-methylated arginine residues in RBM26 RG-repeat motifs indicated it is a substrate for arginine methyltransferases, raising the question of whether this modification regulates its RNA-binding or complex-assembly functions.","evidence":"Immunoprecipitation with MMA-specific antibody, mass spectrometry, and Western blot in EBV-transformed B cells","pmids":["28758620"],"confidence":"Low","gaps":["Single IP/MS identification with no functional follow-up of RBM26 methylation","Methyltransferase responsible not identified","Functional consequence of arginine methylation on RBM26 activity unknown"]},{"year":2020,"claim":"Identification of RBM26 as a component of the PAXT connection answered where RBM26 operates within nuclear RNA surveillance and established it as a limiting factor for exosome-mediated polyadenylated RNA decay.","evidence":"Nuclear pA+-RNA proteome characterization, MTR4-ZFC3H1 complex purification, and siRNA knockdown showing PAXT substrate accumulation","pmids":["31950173"],"confidence":"High","gaps":["Mechanism by which RBM26 recognizes or is recruited to PAXT substrates not defined","Whether RBM26 and RBM27 are redundant or have distinct substrate specificities unknown","Structural basis for RBM26 incorporation into the PAXT complex not determined"]},{"year":2023,"claim":"Demonstrating that PABPN1 recruits RBM26/RBM27 to promote terminal intron splicing revealed a second function for RBM26 beyond RNA decay—connecting it to co-transcriptional splicing regulation.","evidence":"TurboID proximity labeling MS, co-immunoprecipitation, and splicing assays upon siRNA knockdown in HeLa cells","pmids":["37661812"],"confidence":"Medium","gaps":["RBM26-specific interaction domains partly inferred from RBM27 mapping","Full spectrum of splicing events regulated by RBM26 not catalogued","Whether the splicing and PAXT functions of RBM26 are coordinated or independent is unclear"]},{"year":2024,"claim":"Elucidation of ZFC3H1 conformational switching showed that RBM26/27 and ZC3H3 are recruited to 3′ ends of short nuclear RNAs to 'open' ZFC3H1, resolving how PAXT discriminates short RNAs for degradation from longer export-competent transcripts.","evidence":"Co-immunoprecipitation, RNA-seq, domain mutant analysis, and nascent RNA association assays in human cells","pmids":["39461342"],"confidence":"High","gaps":["Precise RNA features that determine RBM26/27 recruitment to 3′ ends not defined","Whether RBM26 directly contacts ZFC3H1 or acts through ZC3H3 intermediary unclear","Structural basis of ZFC3H1 closed-to-open transition not resolved"]},{"year":2024,"claim":"In C. elegans, RBM-26 directly binds mals-1 mRNA to suppress MALSU1 expression, and loss of this regulation causes mitochondrial dysfunction and axon degeneration—revealing a conserved in vivo role in post-transcriptional gene silencing with neurobiological consequences.","evidence":"C. elegans loss-of-function mutants, epistasis with mals-1 double mutants, biochemical RNA-binding screen, axon morphology assays","pmids":["39480871"],"confidence":"High","gaps":["Whether human RBM26 similarly regulates MALSU1 mRNA not tested","Mechanism of mals-1 mRNA repression (degradation vs. translational silencing) not distinguished","Neuronal cell-type specificity and developmental timing of this regulation not fully characterized"]},{"year":2025,"claim":"In fission yeast, the RBM26/27 ortholog Rmn1 interacts with Pab2/PABPN1 and the histone methyltransferase Clr4 and is essential for constitutive heterochromatin formation, suggesting an ancestral link between PAXT-related RNA surveillance and chromatin silencing.","evidence":"Genetic deletion, co-immunoprecipitation, and H3K9me ChIP at centromeres in S. japonicus","pmids":["40163528"],"confidence":"Medium","gaps":["Findings in a distantly related yeast ortholog; conservation in mammals not established","Whether RBM26 contributes to heterochromatin in human cells untested","Mechanism by which Rmn1 bridges RNA processing to histone methylation not resolved"]},{"year":null,"claim":"Key unresolved questions include the structural basis for RBM26 integration into the PAXT complex, whether RBM26 and RBM27 have distinct or fully redundant substrate specificities, and whether the splicing, RNA decay, and potential chromatin functions of RBM26 are mechanistically coordinated.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of RBM26 alone or in complex","Functional distinction between RBM26 and RBM27 not established","Integration of splicing and PAXT decay functions not investigated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,1,2,3,6]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,7]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,2]}],"complexes":["PAXT connection"],"partners":["ZFC3H1","MTR4","ZC3H3","PABPN1","RBM27"],"other_free_text":[]},"mechanistic_narrative":"RBM26 is a nuclear RNA-binding protein that functions as a limiting component of the PAXT (Poly(A) Tail eXosome Targeting) connection, coupling short polyadenylated nuclear RNA recognition to exosome-mediated degradation. Within PAXT, RBM26 (together with its paralog RBM27 and ZC3H3) is recruited to the 3′ ends of short nuclear RNAs, triggering conformational 'opening' of the co-transcriptionally loaded ZFC3H1 scaffold to license exosomal decay, thereby distinguishing short RNAs destined for degradation from longer transcripts routed to nuclear export [PMID:31950173, PMID:39461342]. PABPN1 recruits RBM26/RBM27 to promote splicing of terminal introns harboring weak 3′ splice sites, linking RBM26 to pre-mRNA processing beyond RNA surveillance [PMID:37661812]. In C. elegans, the RBM-26 ortholog directly binds mals-1 mRNA to negatively regulate the MALSU1 mitoribosomal assembly factor, and loss of RBM-26 causes mitochondrial dysfunction and axon degeneration [PMID:39480871]."},"prefetch_data":{"uniprot":{"accession":"Q5T8P6","full_name":"RNA-binding protein 26","aliases":["CTCL tumor antigen se70-2","RNA-binding motif protein 26"],"length_aa":1007,"mass_kda":113.6,"function":"May be involved in the turnover of nuclear polyadenylated (pA+) RNA","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q5T8P6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RBM26","classification":"Not Classified","n_dependent_lines":9,"n_total_lines":1208,"dependency_fraction":0.0074503311258278145},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CALM2","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2},{"gene":"CPSF6","stoichiometry":0.2},{"gene":"DDOST","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2},{"gene":"SRPK2","stoichiometry":0.2},{"gene":"TNPO3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RBM26","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/RBM26"},"hgnc":{"alias_symbol":["PRO1777","SE70-2","FLJ20957","ZC3H17","ARRS2","PPP1R132"],"prev_symbol":["C13orf10"]},"alphafold":{"accession":"Q5T8P6","domains":[{"cath_id":"3.30.70.330","chopping":"532-602","consensus_level":"high","plddt":90.0668,"start":532,"end":602},{"cath_id":"3.30.70.330","chopping":"889-967","consensus_level":"medium","plddt":81.8232,"start":889,"end":967},{"cath_id":"1.20.1390","chopping":"9-77","consensus_level":"high","plddt":85.1557,"start":9,"end":77},{"cath_id":"1.20.58","chopping":"736-791","consensus_level":"medium","plddt":91.1916,"start":736,"end":791}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5T8P6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5T8P6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5T8P6-F1-predicted_aligned_error_v6.png","plddt_mean":57.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RBM26","jax_strain_url":"https://www.jax.org/strain/search?query=RBM26"},"sequence":{"accession":"Q5T8P6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5T8P6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5T8P6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5T8P6"}},"corpus_meta":[{"pmid":"15161670","id":"PMC_15161670","title":"Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas.","date":"2004","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/15161670","citation_count":87,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31950173","id":"PMC_31950173","title":"The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay.","date":"2020","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31950173","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26387816","id":"PMC_26387816","title":"Molecular and Biochemical Characterization of a Novel Xylanase from Massilia sp. 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composition and substrate specificity.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21081503","citation_count":131,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11936,"output_tokens":1552,"usd":0.029544},"stage2":{"model":"claude-opus-4-6","input_tokens":4791,"output_tokens":2048,"usd":0.112732},"total_usd":0.331868,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":23410,"output_tokens":3749,"usd":0.063232},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5653,"output_tokens":2239,"usd":0.12636}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"RBM26 is a component of the PAXT (Poly(A) Tail eXosome Targeting) connection required for nuclear RNA decay. Loss of RBM26 results in accumulation of PAXT substrates (nuclear polyadenylated RNAs), establishing RBM26 as a limiting factor for PAXT-mediated RNA turnover.\",\n      \"method\": \"Nuclear pA+-RNA bound proteome characterization, MTR4-ZFC3H1 complex purification, RNA decay substrate accumulation assays upon RBM26 knockdown\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal complex purification with functional validation (substrate accumulation), replicated across multiple orthogonal methods in a single study\",\n      \"pmids\": [\"31950173\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBM26/27 are transiently recruited to the 3' end of short RNAs with fewer exons, triggering ZFC3H1 'opening' (conformational change) and subsequent exosomal degradation. This establishes RBM26 as a transient PAXT component that senses RNA features to switch ZFC3H1 from a closed (export-permissive) to open (decay-permissive) conformation.\",\n      \"method\": \"Biochemical fractionation, RNA feature analysis, ZFC3H1 conformational studies, loss-of-function with RNA fate readouts\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — mechanistic model supported by multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"39461342\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBM26 and RBM27 are recruited by PABPN1 to promote splicing of last introns with weak 3' splice sites. PABPN1 interacts with the coiled-coil and RRM domain of RBM27 to recruit RBM26/27, facilitating terminal intron splicing.\",\n      \"method\": \"TurboID-MS interactome, PABPN1 depletion with splicing readouts, tethering assays, domain mapping of RBM27-PABPN1 interaction\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (TurboID-MS, tethering, domain mapping, KD phenotype) in a single study\",\n      \"pmids\": [\"37661812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The C. elegans ortholog RBM-26 (RBM26/27) binds the mRNA of the MALS-1 (MALSU1) mitoribosomal assembly factor and negatively regulates its expression. Loss of RBM-26 causes overexpression of MALS-1 protein, leading to mitochondrial dysfunction and axon degeneration; genetic suppression of MALS-1 rescues these defects.\",\n      \"method\": \"Biochemical mRNA binding screen, genetic epistasis (double mutant rescue), loss-of-function mutant phenotypic analysis, Western blot for MALS-1 protein levels\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — biochemical binding screen plus genetic epistasis with clean rescue, multiple orthogonal methods\",\n      \"pmids\": [\"39480871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The fission yeast RBM26/27 ortholog Rmn1 interacts with Pab2/PABPN1 and is essential for heterochromatin formation at centromeres. Rmn1 can interact with the histone H3 Lys9 methyltransferase Clr4, suggesting RBM26/27 orthologs participate in heterochromatin assembly through recruitment of chromatin-modifying factors.\",\n      \"method\": \"Co-immunoprecipitation, genetic deletion with H3K9me2/3 ChIP readouts, protein-protein interaction mapping\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP and genetic deletion with heterochromatin phenotype, but single study in yeast ortholog context\",\n      \"pmids\": [\"40163528\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RBM26 contains mono-methylated arginine (MMA) residues within RG repeat sequences, identified by immunoprecipitation with an MMA-specific antibody (19D4) followed by mass spectrometry in EBV-transformed B-cells, implicating RBM26 as a substrate for arginine methylation.\",\n      \"method\": \"Immunoprecipitation with MMA-specific monoclonal antibody, mass spectrometry, Western blot confirmation\",\n      \"journal\": \"The Journal of general virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — IP-MS identification with Western blot confirmation, single study\",\n      \"pmids\": [\"28758620\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RBM26 is a nuclear RNA-binding protein that functions as a transient component of the PAXT complex, where it is recruited to the 3' ends of short nuclear polyadenylated RNAs to activate ZFC3H1-mediated exosomal decay; it also promotes splicing of terminal introns with weak splice sites via PABPN1 interaction, and in neurons (via its C. elegans ortholog) binds and suppresses MALS-1 mRNA to protect against mitochondrial dysfunction and axon degeneration.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries from KEEP papers.\n\n**Classification:**\n\n- [1] PMID:15161670 — Adenovirus/IFN-gamma in lymphoma. No relation to RBM26. EXCLUDE.\n- [2] PMID:31950173 — ZC3H3 and RBM26/27 in PAXT nuclear RNA decay. KEEP.\n- [3] PMID:26387816 — Xylanase from *Massilia* sp. RBM26 (a bacterial strain, not the gene). EXCLUDE (symbol collision).\n- [4] PMID:37661812 — PABPN1 recruits RBM26/27 to promote splicing. KEEP.\n- [5] PMID:31109875 — β-xylosidase from *Massilia* sp. RBM26. EXCLUDE (symbol collision).\n- [6] PMID:22737227 — Genome-wide profiling; RBM26 mentioned as upregulated in EGCs. No mechanism. EXCLUDE (expression only).\n- [7] PMID:29394417 — GWAS/eQTL for coal workers' pneumoconiosis. EXCLUDE (association only).\n- [8] PMID:34746237 — ceRNA network in ASD; RBM26-AS1 lncRNA. EXCLUDE (alt-locus product + bioinformatics).\n- [9] PMID:28758620 — EBNA2 MMA-RG antibody; RBM26 identified by IP/MS as containing MMA motifs. KEEP (partial).\n- [10] PMID:39389409 — GWAS for tic disorders; RBM26 identified in gene-based analysis. EXCLUDE (association only).\n- [11] PMID:36052691 — ceRNA network in pancreatitis; RBM26-AS1. EXCLUDE (alt-locus product).\n- [12] PMID:39461342 — ZFC3H1 dual modes; RBM26/27 as transient PAXT components. KEEP.\n- [13] PMID:40652529 — RBM26-AS1 encoded micropeptide. EXCLUDE (alt-locus product, case B).\n- [14] PMID:39480871 — C. elegans rbm-26 ortholog of RBM26/27; mechanistic study. KEEP (ortholog).\n- [15] PMID:26365529 — 13q31.1 microdeletion case report; RBM26 mentioned as deleted gene. No mechanism. EXCLUDE.\n- [16] PMID:41441884 — Somatic mutations in CRC; RBM26 mentioned. EXCLUDE (association).\n- [17] PMID:39966283 — RBM26-AS1 micropeptide in liver cancer. EXCLUDE (alt-locus product).\n- [18] PMID:37873356 — Preprint: C. elegans rbm-26 ortholog. KEEP (ortholog, preprint version of PMID:39480871).\n- [19] PMID:40163528 — Fission yeast Pab2/PABPN1; RBM26·27 ortholog Rmn1 involved in heterochromatin. KEEP (ortholog).\n\n**Additional curated papers:**\n- PMID:17081983 — Phosphoproteomics; RBM26 may be in dataset but no specific mechanistic finding described. EXCLUDE.\n- PMID:22658674 — mRNA interactome capture; RBM26 identified as RBP. KEEP (minimal).\n- PMID:12477932, 14702039, 15489334 — cDNA sequencing projects. EXCLUDE (no mechanism).\n- PMID:20562859 — Autophagy network; RBM26 possibly in interactome. No specific finding. EXCLUDE.\n- PMID:26186194, 28514442, 33961781 — BioPlex interactome; RBM26 likely in network. No specific mechanistic finding described in abstract. EXCLUDE.\n- PMID:26496610 — Human interactome; no specific RBM26 finding. EXCLUDE.\n- PMID:25416956 — Proteome-scale interactome. EXCLUDE.\n- PMID:22681889 — mRNA-bound proteome; RBM26 identified as RBP. KEEP (minimal).\n- PMID:29507755 — m6A methyltransferase complex; no RBM26 specific finding. EXCLUDE.\n- PMID:29395067 — BioID of mRNA biology; RBM26 proximity interactions. KEEP (minimal).\n- PMID:35271311 — OpenCell; RBM26 localization data. KEEP (minimal).\n- PMID:26344197 — Metazoan complexes. EXCLUDE (no specific RBM26 finding in abstract).\n- PMID:34079125 — BioID map; RBM26 localization. KEEP (minimal).\n- PMID:19389623 — PP1 interactome; RBM26 identified via RVxF motif. KEEP.\n- PMID:24332808 — PRP19/ATR; no RBM26 specific finding. EXCLUDE.\n- PMID:26673895 — CRM1 export substrates; RBM26 possibly identified. No specific finding in abstract. EXCLUDE.\n- PMID:27565346 — CRL/ARIH1 ubiquitylation; no RBM26 specific finding. EXCLUDE.\n- PMID:21653829 — ASD protein interactome; no specific RBM26 finding described. EXCLUDE.\n- PMID:32807901 — UFMylation/p53; no RBM26 finding. EXCLUDE.\n- PMID:32416067 — BET inhibitors in TNBC; no RBM26 finding. EXCLUDE.\n- PMID:21081503 — PRMT5/RioK1; no RBM26 finding. EXCLUDE.\n- PMID:22939629 — Human protein complexes census. EXCLUDE.\n- PMID:16964243 — Phosphorylation analysis. EXCLUDE.\n- PMID:26912792 — BioID2 method paper. EXCLUDE.\n- PMID:21873635 — GO annotation. EXCLUDE.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"RBM26 and its paralog RBM27 are components of the PAXT (Poly(A) Tail eXosome Targeting) connection required for nuclear polyadenylated RNA decay. Loss of RBM26 leads to accumulation of PAXT substrates, establishing RBM26 as a limiting factor for PAXT-mediated RNA turnover. RBM26 was identified by characterizing nuclear pA+-RNA bound proteomes and MTR4-ZFC3H1-containing complexes.\",\n      \"method\": \"Nuclear pA+-RNA bound proteome characterization, MTR4-ZFC3H1 complex purification under PAXT-assembly-favoring conditions, siRNA knockdown with PAXT substrate accumulation assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal complex purification, loss-of-function with defined substrate accumulation phenotype, replicated with multiple orthogonal methods in single study\",\n      \"pmids\": [\"31950173\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ZFC3H1 is co-transcriptionally loaded onto RNA precursors in a 'closed' conformation that blocks exosome recruitment. For short RNAs with fewer exons, transient PAXT components ZC3H3 and RBM26/27 are preferentially recruited to the 3' end, triggering ZFC3H1 'opening' and subsequent exosomal degradation. This decoupled loading and activation mechanism routes short nuclear RNAs to degradation while longer RNAs with more exons are directed to nuclear export.\",\n      \"method\": \"Co-immunoprecipitation, RNA-seq, knockdown experiments, domain mutant analysis, nascent RNA association assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods establishing pathway position of RBM26/27 in ZFC3H1 activation mechanism\",\n      \"pmids\": [\"39461342\"],\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. PABPN1 interacts with the coiled-coil and RRM domain of RBM27 (and by extension RBM26) to facilitate this recruitment. This function was identified via TurboID-MS interactome analysis of PABPN1 and validated functionally.\",\n      \"method\": \"TurboID proximity labeling mass spectrometry, co-immunoprecipitation, siRNA knockdown, splicing assays in HeLa cells\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — proximity labeling MS plus co-IP and functional splicing assay, but RBM26 finding is partly inferred from RBM27 interaction domain mapping\",\n      \"pmids\": [\"37661812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The C. elegans ortholog RBM-26 (ortholog of human RBM26/27) protects against axon degeneration during neurodevelopment by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor. Loss of RBM-26 causes dramatic overexpression of mals-1 mRNA and MALS-1 protein, and genetic analysis demonstrates that this MALS-1 overexpression is responsible for mitochondrial dysfunction and axon degeneration defects. A biochemical screen identified mals-1 mRNA as a direct binding partner of RBM-26.\",\n      \"method\": \"C. elegans genetics (loss-of-function mutants, epistasis analysis), biochemical RNA-binding screen, immunofluorescence, axon morphology assays\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with double mutant rescue, direct mRNA binding identification, and defined axon degeneration phenotype; ortholog with consistent RNA-binding protein function\",\n      \"pmids\": [\"39480871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In fission yeast Schizosaccharomyces japonicus, the RBM26/27 ortholog Rmn1 interacts with Pab2/PABPN1 and is essential for constitutive heterochromatin formation at centromeres. Rmn1 can interact with the histone H3 Lys9 methyltransferase Clr4, and deletion of the Pab2 N-terminal region (which disrupts its interaction with Rmn1 and ZC3H3 ortholog Red5) largely abolishes Pab2 function in heterochromatin assembly.\",\n      \"method\": \"Genetic deletion analysis, co-immunoprecipitation, ChIP (histone methylation at centromeres), epistasis in fission yeast\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — co-IP and ChIP in ortholog system with deletion phenotype, but findings are in distantly related yeast ortholog\",\n      \"pmids\": [\"40163528\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RBM26 was identified in EBV-transformed B cells as a protein containing mono-methylated arginine (MMA) residues within RG-repeat sequences, co-immunoprecipitated using a monoclonal antibody specific for MMA-modified RG repeats and confirmed by Western blot. This places RBM26 among cellular proteins whose RG repeats serve as arginine methylation substrates.\",\n      \"method\": \"Immunoprecipitation with MMA-specific monoclonal antibody, mass spectrometry, Western blot confirmation\",\n      \"journal\": \"The Journal of general virology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single IP/MS identification with Western blot confirmation; no functional follow-up of RBM26 methylation\",\n      \"pmids\": [\"28758620\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"RBM26 was identified as an mRNA-binding protein (RBP) in human HeLa cells through UV crosslinking and oligo(dT) purification (interactome capture), establishing it as a bona fide component of the human mRNA-bound proteome.\",\n      \"method\": \"UV crosslinking, oligo(dT) purification, quantitative mass spectrometry (interactome capture)\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — large-scale proteomics identification without functional follow-up specific to RBM26\",\n      \"pmids\": [\"22658674\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"BioID proximity labeling of mRNA biology proteins placed RBM26 in the spatial organization of nuclear RNA regulatory structures, with proximity interactions connecting it to mRNA-associated processes.\",\n      \"method\": \"BioID proximity-dependent biotinylation, mass spectrometry\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — proximity labeling without functional validation specific to RBM26\",\n      \"pmids\": [\"29395067\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RBM26 is an RNA-binding protein that functions as a limiting component of the PAXT (Poly(A) Tail eXosome Targeting) connection, where it is recruited to the 3' ends of short nuclear polyadenylated RNAs to trigger ZFC3H1 'opening' and exosome-mediated degradation; additionally, it is recruited by PABPN1 to promote splicing of terminal introns with weak 3' splice sites, contains arginine-methylated RG-repeat motifs, and its C. elegans ortholog directly binds mals-1 mRNA to negatively regulate mitoribosomal assembly factor expression and protect against axon degeneration.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RBM26 is a nuclear RNA-binding protein that functions in RNA quality control and splicing through its roles in the PAXT (Poly(A) Tail eXosome Targeting) connection and PABPN1-dependent terminal intron processing. RBM26 acts as a transient component of the PAXT complex, recruited to the 3' ends of short, exon-poor polyadenylated nuclear RNAs where it triggers a conformational opening of ZFC3H1 that switches RNA fate from export to exosomal decay [PMID:31950173, PMID:39461342]. RBM26 is also recruited by PABPN1 to promote splicing of terminal introns bearing weak 3' splice sites [PMID:37661812]. In C. elegans neurons, the ortholog RBM-26 binds and represses MALS-1 (MALSU1) mRNA, and its loss causes mitochondrial dysfunction and axon degeneration that is rescued by MALS-1 suppression, linking RBM26 to mitochondrial homeostasis and neuronal maintenance [PMID:39480871].\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Identification of RBM26 as an arginine-methylated protein established that it carries post-translational modifications characteristic of RNA-processing factors, but its functional role remained unknown.\",\n      \"evidence\": \"IP with mono-methylarginine-specific antibody followed by mass spectrometry in EBV-transformed B-cells\",\n      \"pmids\": [\"28758620\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of arginine methylation on RBM26 activity is unknown\",\n        \"The methyltransferase(s) responsible were not identified\",\n        \"Single study without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing RBM26 as a component of the PAXT connection answered the key question of where RBM26 acts: it is a limiting factor for nuclear exosome-mediated decay of polyadenylated RNAs, with its depletion causing substrate accumulation.\",\n      \"evidence\": \"Nuclear pA+ RNA-bound proteome characterization, MTR4-ZFC3H1 complex purification, and RNA decay assays upon RBM26 knockdown in human cells\",\n      \"pmids\": [\"31950173\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How RBM26 recognizes its RNA substrates was not resolved\",\n        \"Whether RBM26 is a stable or transient PAXT subunit was unclear\",\n        \"Relationship between RBM26 and its paralog RBM27 was not dissected\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that PABPN1 recruits RBM26/27 to promote splicing of terminal introns with weak 3' splice sites revealed a second, splicing-related function for RBM26 beyond RNA decay, explaining how it interfaces with co-transcriptional RNA processing.\",\n      \"evidence\": \"TurboID-MS interactome, PABPN1 depletion with splicing readouts, tethering assays, and domain mapping of RBM27-PABPN1 interaction\",\n      \"pmids\": [\"37661812\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the splicing and PAXT-decay functions of RBM26 are mutually exclusive or coordinated is unknown\",\n        \"Direct RNA contacts of RBM26 in the splicing context were not mapped\",\n        \"Whether RBM26 and RBM27 have redundant or distinct roles in splicing was not fully resolved\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showing that RBM26/27 transiently associate with the 3' ends of short RNAs to induce ZFC3H1 conformational opening resolved how RNA features are decoded into a decay versus export decision, establishing a mechanistic switch model for PAXT substrate selection.\",\n      \"evidence\": \"Biochemical fractionation, RNA feature analysis, ZFC3H1 conformational studies, and loss-of-function assays with RNA fate readouts in human cells\",\n      \"pmids\": [\"39461342\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis for ZFC3H1 closed-to-open transition upon RBM26 binding is not determined\",\n        \"The precise RNA sequence or structural features sensed by RBM26 at the 3' end are undefined\",\n        \"Whether the transient nature of RBM26 association is regulated remains unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The C. elegans study demonstrated a conserved role for RBM-26 in neuronal homeostasis, showing it suppresses MALS-1 mRNA to maintain mitochondrial function and prevent axon degeneration — the first link between an RBM26 ortholog and neurodegeneration.\",\n      \"evidence\": \"Biochemical mRNA binding screen, genetic epistasis with double-mutant rescue, loss-of-function phenotypic analysis in C. elegans neurons\",\n      \"pmids\": [\"39480871\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether mammalian RBM26 similarly regulates MALSU1 expression has not been tested\",\n        \"The mechanism of MALS-1 mRNA repression (degradation versus translational silencing) is not resolved\",\n        \"Whether this neuronal function is PAXT-dependent or independent is unknown\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstration that fission yeast Rmn1 (RBM26/27 ortholog) interacts with Pab2/PABPN1 and the H3K9 methyltransferase Clr4 to promote centromeric heterochromatin formation extended the functional repertoire of RBM26 orthologs to chromatin regulation.\",\n      \"evidence\": \"Co-immunoprecipitation and genetic deletion with H3K9me2/3 ChIP in S. pombe\",\n      \"pmids\": [\"40163528\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether mammalian RBM26 participates in heterochromatin formation is untested\",\n        \"The Rmn1-Clr4 interaction lacks reciprocal validation or structural detail\",\n        \"Whether the heterochromatin role depends on RNA binding or is independent of it is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of RBM26-ZFC3H1 interaction and conformational switching, the RNA sequence/structural determinants recognized by RBM26, and whether the splicing, decay, and potential chromatin functions are coordinated or context-dependent in mammalian cells.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of RBM26 or its complexes exists\",\n        \"Genome-wide direct RNA binding map (e.g., CLIP) for RBM26 has not been reported\",\n        \"Functional relationship between arginine methylation and RBM26 activity in any pathway is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\n      \"PAXT complex\"\n    ],\n    \"partners\": [\n      \"ZFC3H1\",\n      \"MTR4\",\n      \"PABPN1\",\n      \"RBM27\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"RBM26 is a nuclear RNA-binding protein that functions as a limiting component of the PAXT (Poly(A) Tail eXosome Targeting) connection, coupling short polyadenylated nuclear RNA recognition to exosome-mediated degradation. Within PAXT, RBM26 (together with its paralog RBM27 and ZC3H3) is recruited to the 3′ ends of short nuclear RNAs, triggering conformational 'opening' of the co-transcriptionally loaded ZFC3H1 scaffold to license exosomal decay, thereby distinguishing short RNAs destined for degradation from longer transcripts routed to nuclear export [PMID:31950173, PMID:39461342]. PABPN1 recruits RBM26/RBM27 to promote splicing of terminal introns harboring weak 3′ splice sites, linking RBM26 to pre-mRNA processing beyond RNA surveillance [PMID:37661812]. In C. elegans, the RBM-26 ortholog directly binds mals-1 mRNA to negatively regulate the MALSU1 mitoribosomal assembly factor, and loss of RBM-26 causes mitochondrial dysfunction and axon degeneration [PMID:39480871].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing RBM26 as a bona fide mRNA-binding protein resolved whether its predicted RNA-binding domains were functional in vivo.\",\n      \"evidence\": \"UV crosslinking and oligo(dT) interactome capture in HeLa cells identified RBM26 in the mRNA-bound proteome\",\n      \"pmids\": [\"22658674\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Large-scale proteomics hit without functional follow-up specific to RBM26\",\n        \"RNA targets and binding specificity unknown\",\n        \"No mechanistic context for RBM26 function\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Detection of mono-methylated arginine residues in RBM26 RG-repeat motifs indicated it is a substrate for arginine methyltransferases, raising the question of whether this modification regulates its RNA-binding or complex-assembly functions.\",\n      \"evidence\": \"Immunoprecipitation with MMA-specific antibody, mass spectrometry, and Western blot in EBV-transformed B cells\",\n      \"pmids\": [\"28758620\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single IP/MS identification with no functional follow-up of RBM26 methylation\",\n        \"Methyltransferase responsible not identified\",\n        \"Functional consequence of arginine methylation on RBM26 activity unknown\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identification of RBM26 as a component of the PAXT connection answered where RBM26 operates within nuclear RNA surveillance and established it as a limiting factor for exosome-mediated polyadenylated RNA decay.\",\n      \"evidence\": \"Nuclear pA+-RNA proteome characterization, MTR4-ZFC3H1 complex purification, and siRNA knockdown showing PAXT substrate accumulation\",\n      \"pmids\": [\"31950173\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which RBM26 recognizes or is recruited to PAXT substrates not defined\",\n        \"Whether RBM26 and RBM27 are redundant or have distinct substrate specificities unknown\",\n        \"Structural basis for RBM26 incorporation into the PAXT complex not determined\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that PABPN1 recruits RBM26/RBM27 to promote terminal intron splicing revealed a second function for RBM26 beyond RNA decay—connecting it to co-transcriptional splicing regulation.\",\n      \"evidence\": \"TurboID proximity labeling MS, co-immunoprecipitation, and splicing assays upon siRNA knockdown in HeLa cells\",\n      \"pmids\": [\"37661812\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"RBM26-specific interaction domains partly inferred from RBM27 mapping\",\n        \"Full spectrum of splicing events regulated by RBM26 not catalogued\",\n        \"Whether the splicing and PAXT functions of RBM26 are coordinated or independent is unclear\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Elucidation of ZFC3H1 conformational switching showed that RBM26/27 and ZC3H3 are recruited to 3′ ends of short nuclear RNAs to 'open' ZFC3H1, resolving how PAXT discriminates short RNAs for degradation from longer export-competent transcripts.\",\n      \"evidence\": \"Co-immunoprecipitation, RNA-seq, domain mutant analysis, and nascent RNA association assays in human cells\",\n      \"pmids\": [\"39461342\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise RNA features that determine RBM26/27 recruitment to 3′ ends not defined\",\n        \"Whether RBM26 directly contacts ZFC3H1 or acts through ZC3H3 intermediary unclear\",\n        \"Structural basis of ZFC3H1 closed-to-open transition not resolved\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"In C. elegans, RBM-26 directly binds mals-1 mRNA to suppress MALSU1 expression, and loss of this regulation causes mitochondrial dysfunction and axon degeneration—revealing a conserved in vivo role in post-transcriptional gene silencing with neurobiological consequences.\",\n      \"evidence\": \"C. elegans loss-of-function mutants, epistasis with mals-1 double mutants, biochemical RNA-binding screen, axon morphology assays\",\n      \"pmids\": [\"39480871\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether human RBM26 similarly regulates MALSU1 mRNA not tested\",\n        \"Mechanism of mals-1 mRNA repression (degradation vs. translational silencing) not distinguished\",\n        \"Neuronal cell-type specificity and developmental timing of this regulation not fully characterized\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In fission yeast, the RBM26/27 ortholog Rmn1 interacts with Pab2/PABPN1 and the histone methyltransferase Clr4 and is essential for constitutive heterochromatin formation, suggesting an ancestral link between PAXT-related RNA surveillance and chromatin silencing.\",\n      \"evidence\": \"Genetic deletion, co-immunoprecipitation, and H3K9me ChIP at centromeres in S. japonicus\",\n      \"pmids\": [\"40163528\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Findings in a distantly related yeast ortholog; conservation in mammals not established\",\n        \"Whether RBM26 contributes to heterochromatin in human cells untested\",\n        \"Mechanism by which Rmn1 bridges RNA processing to histone methylation not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis for RBM26 integration into the PAXT complex, whether RBM26 and RBM27 have distinct or fully redundant substrate specificities, and whether the splicing, RNA decay, and potential chromatin functions of RBM26 are mechanistically coordinated.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of RBM26 alone or in complex\",\n        \"Functional distinction between RBM26 and RBM27 not established\",\n        \"Integration of splicing and PAXT decay functions not investigated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 2, 3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\n      \"PAXT connection\"\n    ],\n    \"partners\": [\n      \"ZFC3H1\",\n      \"MTR4\",\n      \"ZC3H3\",\n      \"PABPN1\",\n      \"RBM27\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}