{"gene":"RBMS1","run_date":"2026-06-14T21:17:05+00:00","timeline":{"discoveries":[{"year":2012,"finding":"miR-383 targets RBMS1 by affecting its mRNA stability, thereby suppressing RBMS1 protein levels. Reduced RBMS1 subsequently lowers c-Myc levels (a downstream target of RBMS1), and forced expression of RBMS1 or c-Myc reverses miR-383-mediated promotion of estradiol release from granulosa cells.","method":"Overexpression and knockdown in mouse granulosa cells, luciferase reporter assay, mRNA stability assay, rescue experiments with forced RBMS1/c-Myc expression","journal":"Molecular endocrinology (Baltimore, Md.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (reporter assay, mRNA stability, rescue experiments) in a single lab","pmids":["22593182"],"is_preprint":false},{"year":2022,"finding":"Rbms1 binds and stabilizes Efr3a mRNA in neuronal progenitors of the developing neocortex. Loss of Rbms1 delays the multipolar-to-bipolar transition and radial migration of neuronal progenitors, and ectopic Efr3a rescues the migration defect caused by Rbms1 knockdown both in vivo and in vitro.","method":"In utero electroporation knockdown, cross-linked RNA immunoprecipitation sequencing (CLIP-seq/RIP-seq), qRT-PCR, in vivo and in vitro migration assays, rescue by Efr3a overexpression","journal":"Molecules and cells","confidence":"High","confidence_rationale":"Tier 2 / Strong — RIP-seq identification of binding target plus functional rescue with orthogonal in vivo and in vitro validation","pmids":["35754370"],"is_preprint":false},{"year":2023,"finding":"RBMS1 overexpression inhibits hepatocellular carcinoma cell growth by attenuating GPX4 expression and facilitating ferroptosis in vitro and in vivo. The circIDE/miR-19b-3p/RBMS1 axis regulates ferroptosis: circIDE sponges miR-19b-3p to elevate RBMS1 levels, and reduced RBMS1 (via miR-19b-3p targeting) suppresses ferroptosis.","method":"Overexpression and knockdown in HCC cells, in vitro and in vivo tumor models, circRNA sponge assays","journal":"Epigenetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function and gain-of-function with defined ferroptosis phenotype readout (GPX4 levels, in vivo tumor model), single lab","pmids":["36989117"],"is_preprint":false},{"year":2023,"finding":"RBMS1 promotes ferroptosis resistance in colorectal cancer cells by inducing prion protein (PRNP) translation, thereby conferring resistance to oxaliplatin. Inhibiting RBMS1 reduces PRNP levels, restores ferroptosis sensitivity, and re-sensitizes cells to oxaliplatin.","method":"siRNA knockdown and overexpression in colorectal cancer cells, in vivo and in vitro models, western blot for PRNP, ferroptosis and drug sensitivity assays","journal":"Molecular carcinogenesis","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo and in vitro functional experiments with defined molecular mechanism (PRNP induction), single lab","pmids":["37861356"],"is_preprint":false},{"year":2025,"finding":"RBMS1 promotes pulmonary fibrosis by binding the 3' UTR of Sumo2 mRNA and enhancing its stability, which elevates SUMO2 protein and promotes SUMOylation of Smad4 at lysine 158, thereby activating downstream fibrogenic signaling. Fibroblast-specific Rbms1 deletion reduces bleomycin-induced fibrosis in mice, and pharmacological inhibition by nortriptyline phenocopies this effect.","method":"RNA immunoprecipitation, RNA pull-down, mRNA stability assay, fibroblast-specific knockout mouse model, overexpression mouse model, bleomycin fibrosis model, site-directed mutagenesis (K158), siRNA knockdown","journal":"The European respiratory journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — RIP/pull-down identifying direct mRNA binding, mutagenesis of SUMOylation site, orthogonal in vivo genetic and pharmacological models","pmids":["40473311"],"is_preprint":false},{"year":2026,"finding":"RBMS1 drives cardiac fibrosis by binding to intron 19 of LMO7 pre-mRNA and splicing out exon 20, generating the LMO7-Δe20 isoform. LMO7-Δe20 activates the TGF-β1 pathway by upregulating activator protein 1, promoting fibroblast activation and heart failure. Fibroblast-specific RBMS1 ablation or pharmacological inhibition with nortriptyline or antisense oligonucleotides alleviates this fibrosis.","method":"RNA immunoprecipitation combined with RNA pull-down, unbiased RNA sequencing, fibroblast-specific knockout mice, LMO7-Δe20 overexpression model, TGF-β1 pathway inhibitor (SB431542), antisense oligonucleotides, human cardiac fibroblasts","journal":"European heart journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — RIP and RNA pull-down identifying direct pre-mRNA binding, alternative splicing mechanism defined, multiple orthogonal genetic and pharmacological in vivo models","pmids":["40471706"],"is_preprint":false},{"year":2026,"finding":"RBMS1 directly binds the coding region of ANXA8 (Annexin A8) mRNA via its RRM2 domain, enhancing ANXA8 transcript stability. Elevated ANXA8 activates PI3K/AKT signaling to promote fibroblast activation and renal fibrosis. Fibroblast-specific RBMS1 knockout or nortriptyline treatment reduces renal fibrosis in UUO mice.","method":"RNA-seq, RNA immunoprecipitation (RIP), mRNA stability assay, domain-mapping (RRM2), siRNA knockdown, fibroblast-specific conditional knockout mice, UUO fibrosis model, ANXA8 overexpression/knockdown rescue experiments","journal":"International journal of biological macromolecules","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — RIP with domain identification (RRM2), mRNA stability assay, in vivo conditional knockout, multiple orthogonal rescue experiments in single rigorous study","pmids":["42184845"],"is_preprint":false},{"year":2025,"finding":"RBMS1 promotes glioma cell proliferation by upregulating SSH1 through induction of c-Myc binding to SSH1 promoters. RBMS1 overexpression increases c-Myc activity, which transcriptionally activates SSH1, and this RBMS1–c-Myc–SSH1 axis drives tumor growth in xenograft models.","method":"Glioma cell lines, patient datasets, mouse xenograft models, chromatin immunoprecipitation (ChIP) for c-Myc binding to SSH1 promoter, overexpression and knockdown","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP assay for direct promoter binding plus in vivo xenograft, single lab","pmids":["40120347"],"is_preprint":false},{"year":2023,"finding":"RBMS1 knockdown in pre-adipocytes impairs differentiation and reduces expression of key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affects genes involved in carbohydrate and lipid metabolism, implicating RBMS1 in adipocyte differentiation and metabolism.","method":"siRNA knockdown in 3T3-L1 pre-adipocytes, transcriptomics, proteomics, adipogenic differentiation assays","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined differentiation phenotype and multi-omics, single lab","pmids":["37511060"],"is_preprint":false},{"year":2026,"finding":"YTHDC2 binds RBMS1 mRNA transcripts and promotes their degradation via its m6A-reader function. In ulcerative colitis, YTHDC2 is downregulated, leading to increased RBMS1 mRNA stability, elevated RBMS1 protein, and enhanced ferroptosis in colonic epithelial cells. YTHDC2 overexpression reduces RBMS1 levels and attenuates disease, whereas concurrent RBMS1 overexpression reverses these protective effects.","method":"RNA immunoprecipitation (RIP), mRNA stability assays, western blot, siRNA knockdown and overexpression in colonic epithelial cells, dextran sulfate sodium murine colitis model","journal":"Inflammation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP confirming direct binding, mRNA stability assay, in vivo rescue epistasis, single lab","pmids":["41811549"],"is_preprint":false},{"year":2026,"finding":"The transcription factor ETV1 directly transcriptionally activates RBMS1 expression. RBMS1 knockdown abolishes the pro-tumorigenic effects of ETV1 overexpression in multiple myeloma cells and reverses ETV1-driven M2 polarization of tumor-associated macrophages.","method":"Luciferase reporter assay, chromatin immunoprecipitation (ChIP), gain-of-function/loss-of-function in MM cell lines, in vivo fluorescence imaging, flow cytometry","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and luciferase reporter for direct promoter binding, epistasis rescue experiments, single lab","pmids":["41689098"],"is_preprint":false},{"year":2018,"finding":"Linear CDKN2B-AS1 (ANRIL) transcripts directly bind RBMS1 mRNA by RNA immunoprecipitation and trans-regulate RBMS1 expression at the transcript and protein level, independent of cis-regulatory effects or the circular ANRIL isoforms.","method":"Inducible shRNA knockdown of CDKN2B-AS1, genome-wide mRNA expression, RNA immunoprecipitation (RIP), stable-transfected HeLa cells and HEK293 cells","journal":"European journal of human genetics : EJHG","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP demonstrating direct RNA–RNA interaction, validated in two independent cell types, single lab","pmids":["30108282"],"is_preprint":false},{"year":2024,"finding":"RBMS1 is identified as a dynamically expressed regulator of RNA stabilization in growth cones of callosal projection neurons that is required for successful callosal circuit formation during neocortical development.","method":"Growth cone transcriptome profiling (localized transcriptomics), developmental stage comparisons; mechanistic detail limited in abstract","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptomic localization study; mechanistic details are limited to correlation and inference in the abstract","pmids":["38328182"],"is_preprint":true}],"current_model":"RBMS1 is an RNA-binding protein that stabilizes or regulates the alternative splicing of specific target mRNAs (including Efr3a, Sumo2, ANXA8, and LMO7 pre-mRNA) via its RRM domains, thereby modulating downstream signaling pathways (TGF-β1/Smad4-SUMOylation, PI3K/AKT, c-Myc/SSH1) to control fibroblast activation and fibrosis, neuronal migration and differentiation, ferroptosis resistance, and tumor cell proliferation; its expression is regulated upstream by miR-383 (mRNA stability), YTHDC2 (m6A-dependent mRNA degradation), the lncRNA CDKN2B-AS1 (direct RNA binding in trans), and the transcription factor ETV1 (direct promoter activation)."},"narrative":{"mechanistic_narrative":"RBMS1 is a sequence-specific RNA-binding protein that post-transcriptionally controls the stability and splicing of target transcripts to drive fibroblast activation, tissue fibrosis, neuronal development, and tumor cell behavior [PMID:40473311, PMID:40471706, PMID:42184845, PMID:35754370]. In fibrosis, RBMS1 acts through multiple distinct mRNA targets in an organ-specific manner: it binds the 3' UTR of Sumo2 mRNA to stabilize it and elevate SUMO2, driving SUMOylation of Smad4 at lysine 158 and fibrogenic signaling in lung [PMID:40473311]; it binds intron 19 of LMO7 pre-mRNA and splices out exon 20 to generate the LMO7-Δe20 isoform that activates TGF-β1/AP-1 signaling in cardiac fibroblasts [PMID:40471706]; and it binds the coding region of ANXA8 mRNA via its RRM2 domain to enhance ANXA8 stability and activate PI3K/AKT signaling in renal fibrosis [PMID:42184845]. In each setting, fibroblast-specific Rbms1 deletion and pharmacological inhibition with nortriptyline reduce fibrosis, defining RBMS1 as a convergent, druggable fibrosis driver [PMID:40473311, PMID:40471706, PMID:42184845]. During neocortical development, RBMS1 binds and stabilizes Efr3a mRNA to enable the multipolar-to-bipolar transition and radial migration of neuronal progenitors [PMID:35754370]. In cancer, RBMS1 has context-dependent roles, promoting ferroptosis through attenuated GPX4 in hepatocellular carcinoma [PMID:36989117] yet conferring ferroptosis resistance via PRNP translation in colorectal cancer [PMID:37861356], and driving glioma proliferation through a c-Myc/SSH1 axis [PMID:40120347]. RBMS1 abundance is itself tightly controlled: miR-383 destabilizes its mRNA [PMID:22593182], YTHDC2 promotes m6A-dependent degradation of RBMS1 transcripts [PMID:41811549], the lncRNA CDKN2B-AS1 binds RBMS1 mRNA in trans [PMID:30108282], and the transcription factor ETV1 directly activates the RBMS1 promoter [PMID:41689098].","teleology":[{"year":2012,"claim":"Established that RBMS1 is a post-transcriptionally regulated node whose levels control a downstream effector, linking miR-383 suppression of RBMS1 to reduced c-Myc and altered steroidogenesis.","evidence":"Overexpression/knockdown, luciferase reporter, mRNA stability and rescue assays in mouse granulosa cells","pmids":["22593182"],"confidence":"Medium","gaps":["Direct RNA targets of RBMS1 not identified","Mechanism by which RBMS1 controls c-Myc not resolved"]},{"year":2018,"claim":"Showed that RBMS1 expression is regulated upstream by a long noncoding RNA acting in trans, distinguishing direct RNA-RNA interaction from cis effects.","evidence":"Inducible shRNA knockdown of CDKN2B-AS1 with RIP in HeLa and HEK293 cells","pmids":["30108282"],"confidence":"Medium","gaps":["Functional consequence of CDKN2B-AS1/RBMS1 interaction unclear","No downstream RBMS1 targets defined in this context"]},{"year":2022,"claim":"Provided the first direct binding target and in vivo function, defining RBMS1 as an mRNA-stabilizing factor required for neuronal migration via Efr3a.","evidence":"In utero electroporation knockdown, CLIP-seq/RIP-seq, migration assays and Efr3a rescue in developing neocortex","pmids":["35754370"],"confidence":"High","gaps":["RNA sequence/structural determinants of binding not defined","Generality of stabilization mechanism beyond Efr3a unknown"]},{"year":2023,"claim":"Revealed context-dependent and opposing roles of RBMS1 in cancer ferroptosis, promoting ferroptosis via GPX4 attenuation in HCC but conferring ferroptosis/oxaliplatin resistance via PRNP translation in colorectal cancer, and identified additional pre-adipocyte differentiation roles.","evidence":"Gain/loss-of-function with ferroptosis and drug-sensitivity assays in HCC and CRC cells; siRNA with multi-omics in 3T3-L1 pre-adipocytes","pmids":["36989117","37861356","37511060"],"confidence":"Medium","gaps":["Molecular basis of opposite ferroptosis outcomes across tissues unresolved","Direct RBMS1 binding to GPX4 or PRNP transcripts not demonstrated"]},{"year":2025,"claim":"Defined RBMS1 as a direct fibrosis driver by mapping its binding to the Sumo2 3' UTR, linking transcript stabilization to Smad4 K158 SUMOylation, and validating a druggable axis in lung.","evidence":"RIP/pull-down, mRNA stability, K158 mutagenesis, fibroblast-specific knockout, bleomycin model and nortriptyline treatment","pmids":["40473311"],"confidence":"High","gaps":["RNA motif recognized in Sumo2 3' UTR not defined","Whether RBMS1 directly engages the SUMOylation machinery unknown"]},{"year":2025,"claim":"Extended RBMS1's role to glioma proliferation through a c-Myc–SSH1 transcriptional axis.","evidence":"Glioma cell lines, ChIP for c-Myc at SSH1 promoter, xenografts, overexpression/knockdown","pmids":["40120347"],"confidence":"Medium","gaps":["How RBMS1 increases c-Myc activity mechanistically not established","Direct RBMS1 RNA targets in glioma not identified"]},{"year":2026,"claim":"Demonstrated RBMS1 acts as a splicing regulator in cardiac fibrosis, binding LMO7 pre-mRNA intron 19 to generate a pro-fibrotic LMO7-Δe20 isoform driving TGF-β1/AP-1 signaling.","evidence":"RIP/RNA pull-down, RNA-seq, fibroblast-specific knockout mice, isoform overexpression, SB431542, antisense oligonucleotides, human cardiac fibroblasts","pmids":["40471706"],"confidence":"High","gaps":["Splicing machinery cofactors recruited by RBMS1 unknown","Determinants of target-specific stabilization versus splicing activity unresolved"]},{"year":2026,"claim":"Mapped RBMS1's coding-region binding to ANXA8 mRNA to a specific RRM2 domain, stabilizing the transcript to activate PI3K/AKT in renal fibrosis and reinforcing nortriptyline as a cross-organ anti-fibrotic.","evidence":"RNA-seq, RIP, mRNA stability, RRM2 domain mapping, fibroblast-specific knockout, UUO model, ANXA8 rescue","pmids":["42184845"],"confidence":"High","gaps":["Contributions of RRM1 versus RRM2 to other targets not delineated","Structural basis of coding-region recognition not solved"]},{"year":2026,"claim":"Identified upstream regulators that set RBMS1 abundance — YTHDC2-mediated m6A-dependent degradation in ulcerative colitis and ETV1-driven promoter activation in multiple myeloma — placing RBMS1 within m6A and transcriptional control circuits.","evidence":"RIP, mRNA stability, DSS colitis model (YTHDC2); luciferase, ChIP, epistasis and xenograft (ETV1)","pmids":["41811549","41689098"],"confidence":"Medium","gaps":["m6A sites on RBMS1 mRNA not mapped","Whether these upstream regulators converge on shared RBMS1 functions unknown"]},{"year":null,"claim":"How a single RNA-binding protein selects between mRNA stabilization and alternative splicing, and what dictates its opposing ferroptosis and proliferation outcomes across tissues, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying RNA recognition motif or structural model across targets","No proteomic partner map linking RBMS1 to splicing or decay machinery","Cause of tissue-specific functional polarity not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1,4,5,6]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[5]}],"localization":[],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[1,4,5,6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,5,6]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[2,3]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P29558","full_name":"RNA-binding motif, single-stranded-interacting protein 1","aliases":["Single-stranded DNA-binding protein MSSP-1","Suppressor of CDC2 with RNA-binding motif 2"],"length_aa":406,"mass_kda":44.5,"function":"Single-stranded DNA binding protein that interacts with the region upstream of the MYC gene. Binds specifically to the DNA sequence motif 5'-[AT]CT[AT][AT]T-3'. Probably has a role in DNA replication","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P29558/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RBMS1","classification":"Not Classified","n_dependent_lines":12,"n_total_lines":1208,"dependency_fraction":0.009933774834437087},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RBMS1","total_profiled":1310},"omim":[{"mim_id":"613149","title":"CDKN2B ANTISENSE RNA; CDKN2BAS","url":"https://www.omim.org/entry/613149"},{"mim_id":"602310","title":"RNA-BINDING MOTIF PROTEIN, SINGLE STRAND-INTERACTING, 1; RBMS1","url":"https://www.omim.org/entry/602310"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RBMS1"},"hgnc":{"alias_symbol":["SCR2","MSSP-1","MSSP-2","MSSP-3","YC1","HCC-4","DKFZp564H0764"],"prev_symbol":["C2orf12"]},"alphafold":{"accession":"P29558","domains":[{"cath_id":"3.30.70.330","chopping":"56-131","consensus_level":"high","plddt":93.8936,"start":56,"end":131},{"cath_id":"3.30.70.330","chopping":"141-222","consensus_level":"high","plddt":91.8121,"start":141,"end":222}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P29558","model_url":"https://alphafold.ebi.ac.uk/files/AF-P29558-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P29558-F1-predicted_aligned_error_v6.png","plddt_mean":64.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RBMS1","jax_strain_url":"https://www.jax.org/strain/search?query=RBMS1"},"sequence":{"accession":"P29558","fasta_url":"https://rest.uniprot.org/uniprotkb/P29558.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P29558/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P29558"}},"corpus_meta":[{"pmid":"22593182","id":"PMC_22593182","title":"Transactivation of microRNA-383 by steroidogenic factor-1 promotes estradiol release from mouse ovarian granulosa cells by targeting RBMS1.","date":"2012","source":"Molecular endocrinology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/22593182","citation_count":103,"is_preprint":false},{"pmid":"23810756","id":"PMC_23810756","title":"MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2.","date":"2013","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/23810756","citation_count":95,"is_preprint":false},{"pmid":"23169919","id":"PMC_23169919","title":"The novel proteasome inhibitor BSc2118 protects against cerebral ischaemia through HIF1A accumulation and enhanced angioneurogenesis.","date":"2012","source":"Brain : a journal of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/23169919","citation_count":57,"is_preprint":false},{"pmid":"36989117","id":"PMC_36989117","title":"Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.","date":"2023","source":"Epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/36989117","citation_count":38,"is_preprint":false},{"pmid":"30108282","id":"PMC_30108282","title":"Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer binding factor RBMS1.","date":"2018","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/30108282","citation_count":37,"is_preprint":false},{"pmid":"37861356","id":"PMC_37861356","title":"Inhibition of the RBMS1/PRNP axis improves ferroptosis resistance-mediated oxaliplatin chemoresistance in colorectal cancer.","date":"2023","source":"Molecular carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/37861356","citation_count":16,"is_preprint":false},{"pmid":"35754370","id":"PMC_35754370","title":"RNA Binding Protein Rbms1 Enables Neuronal Differentiation and Radial Migration during Neocortical Development by Binding and Stabilizing the RNA Message for Efr3a.","date":"2022","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/35754370","citation_count":12,"is_preprint":false},{"pmid":"24928548","id":"PMC_24928548","title":"Gene expression analysis in MCF-7 breast cancer cells treated with recombinant bromelain.","date":"2014","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/24928548","citation_count":11,"is_preprint":false},{"pmid":"40471706","id":"PMC_40471706","title":"Deficiency of the RNA-binding protein RBMS1 improves myocardial fibrosis and heart failure.","date":"2026","source":"European heart journal","url":"https://pubmed.ncbi.nlm.nih.gov/40471706","citation_count":9,"is_preprint":false},{"pmid":"37511060","id":"PMC_37511060","title":"Transcriptomic and Proteomic Analysis Reveals the Potential Role of RBMS1 in Adipogenesis and Adipocyte Metabolism.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37511060","citation_count":8,"is_preprint":false},{"pmid":"25037273","id":"PMC_25037273","title":"Functional analysis and molecular characterization of spontaneously outgrown human lymphoblastoid cell lines.","date":"2014","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/25037273","citation_count":5,"is_preprint":false},{"pmid":"38328182","id":"PMC_38328182","title":"Dynamic subtype- and context-specific subcellular RNA regulation in growth cones of developing neurons of the cerebral cortex.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38328182","citation_count":4,"is_preprint":false},{"pmid":"40473311","id":"PMC_40473311","title":"Rbms1 promotes pulmonary fibrosis by stabilising Sumo2 mRNA to facilitate Smad4-SUMOylation and fibroblast activation.","date":"2025","source":"The European respiratory journal","url":"https://pubmed.ncbi.nlm.nih.gov/40473311","citation_count":2,"is_preprint":false},{"pmid":"40629190","id":"PMC_40629190","title":"Expression profile and prognostic relevance of immune infiltration-related RBMS1 in gliomas: a multidimensional integrative analysis.","date":"2025","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40629190","citation_count":1,"is_preprint":false},{"pmid":"40747376","id":"PMC_40747376","title":"Identification of key ferroptosis-related genes associated with the development of gastric cancer: Prognostic models, molecular mechanisms and potential treatment strategies.","date":"2025","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/40747376","citation_count":1,"is_preprint":false},{"pmid":"42184845","id":"PMC_42184845","title":"RNA binding motif single-stranded interacting protein 1 drives renal fibrosis by stabilizing Annexin A8 mRNA to activate PI3K/AKT signaling.","date":"2026","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/42184845","citation_count":0,"is_preprint":false},{"pmid":"40120347","id":"PMC_40120347","title":"RBMS1 promotes the proliferation of glioma cells via regulation of the c-Myc-SSH1 axis.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/40120347","citation_count":0,"is_preprint":false},{"pmid":"41811549","id":"PMC_41811549","title":"YTHDC2 Deficiency Exacerbates Ulcerative Colitis by Stabilizing RBMS1 mRNA to Drive Epithelial Ferroptosis.","date":"2026","source":"Inflammation","url":"https://pubmed.ncbi.nlm.nih.gov/41811549","citation_count":0,"is_preprint":false},{"pmid":"41689098","id":"PMC_41689098","title":"m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1.","date":"2026","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41689098","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"sonnet_model":"claude-sonnet-4-6","sonnet_input_tokens":13002,"sonnet_output_tokens":3525,"sonnet_usd":0.0919,"sonnet_elapsed_seconds":58.3,"stage1_stop_reason":"end_turn"},"stage2":{"opus_model":"claude-opus-4-8","opus_input_tokens":11193,"opus_output_tokens":3525,"opus_usd":0.1441,"opus_elapsed_seconds":39.1,"stage2_stop_reason":"end_turn"},"total_usd":0.236},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"miR-383 targets RBMS1 by affecting its mRNA stability, thereby suppressing RBMS1 protein levels. Reduced RBMS1 subsequently lowers c-Myc levels (a downstream target of RBMS1), and forced expression of RBMS1 or c-Myc reverses miR-383-mediated promotion of estradiol release from granulosa cells.\",\n      \"method\": \"Overexpression and knockdown in mouse granulosa cells, luciferase reporter assay, mRNA stability assay, rescue experiments with forced RBMS1/c-Myc expression\",\n      \"journal\": \"Molecular endocrinology (Baltimore, Md.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (reporter assay, mRNA stability, rescue experiments) in a single lab\",\n      \"pmids\": [\"22593182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Rbms1 binds and stabilizes Efr3a mRNA in neuronal progenitors of the developing neocortex. Loss of Rbms1 delays the multipolar-to-bipolar transition and radial migration of neuronal progenitors, and ectopic Efr3a rescues the migration defect caused by Rbms1 knockdown both in vivo and in vitro.\",\n      \"method\": \"In utero electroporation knockdown, cross-linked RNA immunoprecipitation sequencing (CLIP-seq/RIP-seq), qRT-PCR, in vivo and in vitro migration assays, rescue by Efr3a overexpression\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RIP-seq identification of binding target plus functional rescue with orthogonal in vivo and in vitro validation\",\n      \"pmids\": [\"35754370\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBMS1 overexpression inhibits hepatocellular carcinoma cell growth by attenuating GPX4 expression and facilitating ferroptosis in vitro and in vivo. The circIDE/miR-19b-3p/RBMS1 axis regulates ferroptosis: circIDE sponges miR-19b-3p to elevate RBMS1 levels, and reduced RBMS1 (via miR-19b-3p targeting) suppresses ferroptosis.\",\n      \"method\": \"Overexpression and knockdown in HCC cells, in vitro and in vivo tumor models, circRNA sponge assays\",\n      \"journal\": \"Epigenetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function and gain-of-function with defined ferroptosis phenotype readout (GPX4 levels, in vivo tumor model), single lab\",\n      \"pmids\": [\"36989117\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBMS1 promotes ferroptosis resistance in colorectal cancer cells by inducing prion protein (PRNP) translation, thereby conferring resistance to oxaliplatin. Inhibiting RBMS1 reduces PRNP levels, restores ferroptosis sensitivity, and re-sensitizes cells to oxaliplatin.\",\n      \"method\": \"siRNA knockdown and overexpression in colorectal cancer cells, in vivo and in vitro models, western blot for PRNP, ferroptosis and drug sensitivity assays\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo and in vitro functional experiments with defined molecular mechanism (PRNP induction), single lab\",\n      \"pmids\": [\"37861356\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBMS1 promotes pulmonary fibrosis by binding the 3' UTR of Sumo2 mRNA and enhancing its stability, which elevates SUMO2 protein and promotes SUMOylation of Smad4 at lysine 158, thereby activating downstream fibrogenic signaling. Fibroblast-specific Rbms1 deletion reduces bleomycin-induced fibrosis in mice, and pharmacological inhibition by nortriptyline phenocopies this effect.\",\n      \"method\": \"RNA immunoprecipitation, RNA pull-down, mRNA stability assay, fibroblast-specific knockout mouse model, overexpression mouse model, bleomycin fibrosis model, site-directed mutagenesis (K158), siRNA knockdown\",\n      \"journal\": \"The European respiratory journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — RIP/pull-down identifying direct mRNA binding, mutagenesis of SUMOylation site, orthogonal in vivo genetic and pharmacological models\",\n      \"pmids\": [\"40473311\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"RBMS1 drives cardiac fibrosis by binding to intron 19 of LMO7 pre-mRNA and splicing out exon 20, generating the LMO7-Δe20 isoform. LMO7-Δe20 activates the TGF-β1 pathway by upregulating activator protein 1, promoting fibroblast activation and heart failure. Fibroblast-specific RBMS1 ablation or pharmacological inhibition with nortriptyline or antisense oligonucleotides alleviates this fibrosis.\",\n      \"method\": \"RNA immunoprecipitation combined with RNA pull-down, unbiased RNA sequencing, fibroblast-specific knockout mice, LMO7-Δe20 overexpression model, TGF-β1 pathway inhibitor (SB431542), antisense oligonucleotides, human cardiac fibroblasts\",\n      \"journal\": \"European heart journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — RIP and RNA pull-down identifying direct pre-mRNA binding, alternative splicing mechanism defined, multiple orthogonal genetic and pharmacological in vivo models\",\n      \"pmids\": [\"40471706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"RBMS1 directly binds the coding region of ANXA8 (Annexin A8) mRNA via its RRM2 domain, enhancing ANXA8 transcript stability. Elevated ANXA8 activates PI3K/AKT signaling to promote fibroblast activation and renal fibrosis. Fibroblast-specific RBMS1 knockout or nortriptyline treatment reduces renal fibrosis in UUO mice.\",\n      \"method\": \"RNA-seq, RNA immunoprecipitation (RIP), mRNA stability assay, domain-mapping (RRM2), siRNA knockdown, fibroblast-specific conditional knockout mice, UUO fibrosis model, ANXA8 overexpression/knockdown rescue experiments\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — RIP with domain identification (RRM2), mRNA stability assay, in vivo conditional knockout, multiple orthogonal rescue experiments in single rigorous study\",\n      \"pmids\": [\"42184845\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBMS1 promotes glioma cell proliferation by upregulating SSH1 through induction of c-Myc binding to SSH1 promoters. RBMS1 overexpression increases c-Myc activity, which transcriptionally activates SSH1, and this RBMS1–c-Myc–SSH1 axis drives tumor growth in xenograft models.\",\n      \"method\": \"Glioma cell lines, patient datasets, mouse xenograft models, chromatin immunoprecipitation (ChIP) for c-Myc binding to SSH1 promoter, overexpression and knockdown\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP assay for direct promoter binding plus in vivo xenograft, single lab\",\n      \"pmids\": [\"40120347\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBMS1 knockdown in pre-adipocytes impairs differentiation and reduces expression of key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affects genes involved in carbohydrate and lipid metabolism, implicating RBMS1 in adipocyte differentiation and metabolism.\",\n      \"method\": \"siRNA knockdown in 3T3-L1 pre-adipocytes, transcriptomics, proteomics, adipogenic differentiation assays\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined differentiation phenotype and multi-omics, single lab\",\n      \"pmids\": [\"37511060\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"YTHDC2 binds RBMS1 mRNA transcripts and promotes their degradation via its m6A-reader function. In ulcerative colitis, YTHDC2 is downregulated, leading to increased RBMS1 mRNA stability, elevated RBMS1 protein, and enhanced ferroptosis in colonic epithelial cells. YTHDC2 overexpression reduces RBMS1 levels and attenuates disease, whereas concurrent RBMS1 overexpression reverses these protective effects.\",\n      \"method\": \"RNA immunoprecipitation (RIP), mRNA stability assays, western blot, siRNA knockdown and overexpression in colonic epithelial cells, dextran sulfate sodium murine colitis model\",\n      \"journal\": \"Inflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP confirming direct binding, mRNA stability assay, in vivo rescue epistasis, single lab\",\n      \"pmids\": [\"41811549\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The transcription factor ETV1 directly transcriptionally activates RBMS1 expression. RBMS1 knockdown abolishes the pro-tumorigenic effects of ETV1 overexpression in multiple myeloma cells and reverses ETV1-driven M2 polarization of tumor-associated macrophages.\",\n      \"method\": \"Luciferase reporter assay, chromatin immunoprecipitation (ChIP), gain-of-function/loss-of-function in MM cell lines, in vivo fluorescence imaging, flow cytometry\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and luciferase reporter for direct promoter binding, epistasis rescue experiments, single lab\",\n      \"pmids\": [\"41689098\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Linear CDKN2B-AS1 (ANRIL) transcripts directly bind RBMS1 mRNA by RNA immunoprecipitation and trans-regulate RBMS1 expression at the transcript and protein level, independent of cis-regulatory effects or the circular ANRIL isoforms.\",\n      \"method\": \"Inducible shRNA knockdown of CDKN2B-AS1, genome-wide mRNA expression, RNA immunoprecipitation (RIP), stable-transfected HeLa cells and HEK293 cells\",\n      \"journal\": \"European journal of human genetics : EJHG\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP demonstrating direct RNA–RNA interaction, validated in two independent cell types, single lab\",\n      \"pmids\": [\"30108282\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBMS1 is identified as a dynamically expressed regulator of RNA stabilization in growth cones of callosal projection neurons that is required for successful callosal circuit formation during neocortical development.\",\n      \"method\": \"Growth cone transcriptome profiling (localized transcriptomics), developmental stage comparisons; mechanistic detail limited in abstract\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptomic localization study; mechanistic details are limited to correlation and inference in the abstract\",\n      \"pmids\": [\"38328182\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"RBMS1 is an RNA-binding protein that stabilizes or regulates the alternative splicing of specific target mRNAs (including Efr3a, Sumo2, ANXA8, and LMO7 pre-mRNA) via its RRM domains, thereby modulating downstream signaling pathways (TGF-β1/Smad4-SUMOylation, PI3K/AKT, c-Myc/SSH1) to control fibroblast activation and fibrosis, neuronal migration and differentiation, ferroptosis resistance, and tumor cell proliferation; its expression is regulated upstream by miR-383 (mRNA stability), YTHDC2 (m6A-dependent mRNA degradation), the lncRNA CDKN2B-AS1 (direct RNA binding in trans), and the transcription factor ETV1 (direct promoter activation).\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RBMS1 is a sequence-specific RNA-binding protein that post-transcriptionally controls the stability and splicing of target transcripts to drive fibroblast activation, tissue fibrosis, neuronal development, and tumor cell behavior [#4, #5, #6, #1]. In fibrosis, RBMS1 acts through multiple distinct mRNA targets in an organ-specific manner: it binds the 3' UTR of Sumo2 mRNA to stabilize it and elevate SUMO2, driving SUMOylation of Smad4 at lysine 158 and fibrogenic signaling in lung [#4]; it binds intron 19 of LMO7 pre-mRNA and splices out exon 20 to generate the LMO7-Δe20 isoform that activates TGF-β1/AP-1 signaling in cardiac fibroblasts [#5]; and it binds the coding region of ANXA8 mRNA via its RRM2 domain to enhance ANXA8 stability and activate PI3K/AKT signaling in renal fibrosis [#6]. In each setting, fibroblast-specific Rbms1 deletion and pharmacological inhibition with nortriptyline reduce fibrosis, defining RBMS1 as a convergent, druggable fibrosis driver [#4, #5, #6]. During neocortical development, RBMS1 binds and stabilizes Efr3a mRNA to enable the multipolar-to-bipolar transition and radial migration of neuronal progenitors [#1]. In cancer, RBMS1 has context-dependent roles, promoting ferroptosis through attenuated GPX4 in hepatocellular carcinoma [#2] yet conferring ferroptosis resistance via PRNP translation in colorectal cancer [#3], and driving glioma proliferation through a c-Myc/SSH1 axis [#7]. RBMS1 abundance is itself tightly controlled: miR-383 destabilizes its mRNA [#0], YTHDC2 promotes m6A-dependent degradation of RBMS1 transcripts [#9], the lncRNA CDKN2B-AS1 binds RBMS1 mRNA in trans [#11], and the transcription factor ETV1 directly activates the RBMS1 promoter [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that RBMS1 is a post-transcriptionally regulated node whose levels control a downstream effector, linking miR-383 suppression of RBMS1 to reduced c-Myc and altered steroidogenesis.\",\n      \"evidence\": \"Overexpression/knockdown, luciferase reporter, mRNA stability and rescue assays in mouse granulosa cells\",\n      \"pmids\": [\"22593182\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct RNA targets of RBMS1 not identified\", \"Mechanism by which RBMS1 controls c-Myc not resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed that RBMS1 expression is regulated upstream by a long noncoding RNA acting in trans, distinguishing direct RNA-RNA interaction from cis effects.\",\n      \"evidence\": \"Inducible shRNA knockdown of CDKN2B-AS1 with RIP in HeLa and HEK293 cells\",\n      \"pmids\": [\"30108282\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of CDKN2B-AS1/RBMS1 interaction unclear\", \"No downstream RBMS1 targets defined in this context\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Provided the first direct binding target and in vivo function, defining RBMS1 as an mRNA-stabilizing factor required for neuronal migration via Efr3a.\",\n      \"evidence\": \"In utero electroporation knockdown, CLIP-seq/RIP-seq, migration assays and Efr3a rescue in developing neocortex\",\n      \"pmids\": [\"35754370\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"RNA sequence/structural determinants of binding not defined\", \"Generality of stabilization mechanism beyond Efr3a unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed context-dependent and opposing roles of RBMS1 in cancer ferroptosis, promoting ferroptosis via GPX4 attenuation in HCC but conferring ferroptosis/oxaliplatin resistance via PRNP translation in colorectal cancer, and identified additional pre-adipocyte differentiation roles.\",\n      \"evidence\": \"Gain/loss-of-function with ferroptosis and drug-sensitivity assays in HCC and CRC cells; siRNA with multi-omics in 3T3-L1 pre-adipocytes\",\n      \"pmids\": [\"36989117\", \"37861356\", \"37511060\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of opposite ferroptosis outcomes across tissues unresolved\", \"Direct RBMS1 binding to GPX4 or PRNP transcripts not demonstrated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined RBMS1 as a direct fibrosis driver by mapping its binding to the Sumo2 3' UTR, linking transcript stabilization to Smad4 K158 SUMOylation, and validating a druggable axis in lung.\",\n      \"evidence\": \"RIP/pull-down, mRNA stability, K158 mutagenesis, fibroblast-specific knockout, bleomycin model and nortriptyline treatment\",\n      \"pmids\": [\"40473311\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"RNA motif recognized in Sumo2 3' UTR not defined\", \"Whether RBMS1 directly engages the SUMOylation machinery unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended RBMS1's role to glioma proliferation through a c-Myc–SSH1 transcriptional axis.\",\n      \"evidence\": \"Glioma cell lines, ChIP for c-Myc at SSH1 promoter, xenografts, overexpression/knockdown\",\n      \"pmids\": [\"40120347\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How RBMS1 increases c-Myc activity mechanistically not established\", \"Direct RBMS1 RNA targets in glioma not identified\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated RBMS1 acts as a splicing regulator in cardiac fibrosis, binding LMO7 pre-mRNA intron 19 to generate a pro-fibrotic LMO7-Δe20 isoform driving TGF-β1/AP-1 signaling.\",\n      \"evidence\": \"RIP/RNA pull-down, RNA-seq, fibroblast-specific knockout mice, isoform overexpression, SB431542, antisense oligonucleotides, human cardiac fibroblasts\",\n      \"pmids\": [\"40471706\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Splicing machinery cofactors recruited by RBMS1 unknown\", \"Determinants of target-specific stabilization versus splicing activity unresolved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Mapped RBMS1's coding-region binding to ANXA8 mRNA to a specific RRM2 domain, stabilizing the transcript to activate PI3K/AKT in renal fibrosis and reinforcing nortriptyline as a cross-organ anti-fibrotic.\",\n      \"evidence\": \"RNA-seq, RIP, mRNA stability, RRM2 domain mapping, fibroblast-specific knockout, UUO model, ANXA8 rescue\",\n      \"pmids\": [\"42184845\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Contributions of RRM1 versus RRM2 to other targets not delineated\", \"Structural basis of coding-region recognition not solved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified upstream regulators that set RBMS1 abundance — YTHDC2-mediated m6A-dependent degradation in ulcerative colitis and ETV1-driven promoter activation in multiple myeloma — placing RBMS1 within m6A and transcriptional control circuits.\",\n      \"evidence\": \"RIP, mRNA stability, DSS colitis model (YTHDC2); luciferase, ChIP, epistasis and xenograft (ETV1)\",\n      \"pmids\": [\"41811549\", \"41689098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"m6A sites on RBMS1 mRNA not mapped\", \"Whether these upstream regulators converge on shared RBMS1 functions unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single RNA-binding protein selects between mRNA stabilization and alternative splicing, and what dictates its opposing ferroptosis and proliferation outcomes across tissues, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No unifying RNA recognition motif or structural model across targets\", \"No proteomic partner map linking RBMS1 to splicing or decay machinery\", \"Cause of tissue-specific functional polarity not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1, 4, 5, 6]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [1, 4, 5, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 5, 6]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win"}}