{"gene":"RBM47","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2014,"finding":"RBM47 binds broadly to mRNAs (most prominently in introns and 3'UTRs) as revealed by transcriptome-wide HITS-CLIP, and alters splicing and abundance of a subset of target mRNAs; one mechanism of tumor suppression involves stabilization of DKK1 mRNA to inhibit Wnt signaling and breast cancer progression.","method":"HITS-CLIP (transcriptome-wide), mRNA stability assays, functional breast cancer models","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — transcriptome-wide HITS-CLIP with multiple functional validations in a single rigorous study","pmids":["24898756"],"is_preprint":false},{"year":2014,"finding":"RBM47 interacts with APOBEC1 and A1CF, can substitute for A1CF, and is necessary and sufficient for APOBEC1-mediated C-to-U RNA editing in vitro; Rbm47-deficient mice show impaired C-to-U RNA editing.","method":"Co-immunoprecipitation, in vitro RNA editing reconstitution assay, Rbm47 mutant mouse model","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution plus genetic loss-of-function in mice, independently consistent with subsequent studies","pmids":["24916387"],"is_preprint":false},{"year":2018,"finding":"In mouse intestine and liver, RBM47 and A1CF function independently yet interact in a tissue-specific manner to regulate APOBEC1-dependent C-to-U RNA editing site selection; intestine-specific Rbm47 knockout nearly eliminates apoB RNA editing (<6%), while liver-specific knockout reduces editing of a subset of targets; double knockout of both A1cf and Rbm47 eliminates apoB RNA editing in liver.","method":"Tissue-specific conditional knockout mice (liver-specific and intestine-specific), RNA editing quantification of multiple targets","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean tissue-specific KO with defined molecular phenotype, replicated across tissues and cofactor combinations","pmids":["30309881"],"is_preprint":false},{"year":2019,"finding":"RBM47 promotes inclusion of exon 20 (α-domain) of TJP1 pre-mRNA by recognizing (U)GCAUG sequences in the downstream intronic region; the first RRM domain of RBM47 is critical for this alternative splicing regulation. Loss of RBM47-mediated inclusion yields a TJP1-α− isoform that enhances actin stress fiber assembly and promotes cell migration.","method":"Splicing reporter assays, RRM domain mutagenesis, RNA binding assays, wound healing/migration assays","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — mutagenesis of RRM domain, direct RNA binding, functional migration readout in single rigorous study","pmids":["31358901"],"is_preprint":false},{"year":2019,"finding":"RBM47 regulates p53 at the transcriptional level: RBM47 knockdown reduces p53 mRNA and protein by impairing p53 promoter activity, and RBM47 overexpression enhances p53 promoter activity. By controlling p53, RBM47 concomitantly controls p21WAF1/CIP1 expression at the transcriptional level, acting as a molecular switch between cell death and senescence after DNA damage.","method":"siRNA knockdown, Flag-RBM47 overexpression, luciferase promoter activity assays, Western blot, RT-PCR","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — promoter activity assays with OE and KD, single lab, two orthogonal methods","pmids":["31511650"],"is_preprint":false},{"year":2019,"finding":"APOBEC1-RBM47 and APOBEC1-A1CF complexes reconstituted in HEK293T cells show differential RNA editing activity across multiple target RNAs; the minimal domain requirement of RBM47 for editing activity was determined, and clear species differences (mouse vs. human) were observed.","method":"Cell-based fluorescence RNA editing assay (eGFP subcellular localization), domain truncation/mutagenesis, reconstitution in HEK293T cells","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cell-based reconstitution with domain mutagenesis, multiple RNA targets tested, direct biochemical evidence","pmids":["30844405"],"is_preprint":false},{"year":2018,"finding":"RBM47 promotes IL-10 mRNA stability in B cells by binding to AU-rich elements in the 3'UTR of Il10 mRNA, thereby elevating IL-10 production and enhancing immunosuppressive B cell function including Foxp3+ Treg induction.","method":"mRNA microarray, RNA immunoprecipitation (RIP), mRNA stability assay, overexpression functional assays","journal":"Cellular & molecular immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus mRNA stability assay plus functional readout, single lab","pmids":["29844590"],"is_preprint":false},{"year":2020,"finding":"RBM47 binds the AXIN1 mRNA and stabilizes it, thereby enhancing suppression of Wnt/β-catenin signaling in NSCLC cells; lentiviral knockdown of RBM47 reduces AXIN1 levels and promotes proliferation, migration, and invasion.","method":"RNA immunoprecipitation, mRNA stability assay, lentiviral knockdown, in vitro and in vivo functional assays","journal":"Surgical oncology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus mRNA stability plus in vivo tumor model, single lab","pmids":["32891348"],"is_preprint":false},{"year":2021,"finding":"RBM47 binds the 3'UTR of IFNAR1 mRNA, increases its stability, and retards IFNAR1 degradation, thereby enhancing IFN-stimulated gene expression and broad-spectrum antiviral activity; RBM47 expression is induced by viral infection or interferon stimulation and has no noticeable impact on IFN production itself.","method":"RNA immunoprecipitation, mRNA stability assay, multiple virus infection models in vitro and in vivo, ISRE reporter assay","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal RNA-IP, mRNA stability, in vitro and in vivo virus models, multiple orthogonal methods","pmids":["34160127"],"is_preprint":false},{"year":2021,"finding":"RBM47 binds to the promoter of BCAT1 and regulates its transcription in NPC cells; RBM47 also cooperates with hnRNPM (confirmed by co-immunoprecipitation) to regulate alternative splicing of multiple pre-mRNAs.","method":"ChIP (chromatin immunoprecipitation), transcriptome analysis, Co-IP with hnRNPM, functional knockdown assays","journal":"Journal of genetics and genomics","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — ChIP for promoter binding and Co-IP for hnRNPM interaction, single lab with two orthogonal methods","pmids":["34274258"],"is_preprint":false},{"year":2020,"finding":"Zebrafish RBM47 interacts with MAVS and promotes its lysosome-dependent degradation, changing MAVS cellular localization from cytoplasm to the lysosome region, thereby inhibiting downstream MITA and IRF3/7 activation and suppressing IFN production.","method":"Co-immunoprecipitation, subcellular localization assays, lysosome inhibitor experiments, functional IFN reporter assays","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP, localization with functional consequence, pathway epistasis, single lab","pmids":["32859727"],"is_preprint":false},{"year":2013,"finding":"Human RBM47 specifically binds RNA but not single-stranded DNA; zebrafish rbm47 knockdown causes headless/small head phenotypes rescued by wnt8a morpholino, placing rbm47 function upstream of Wnt8a signaling in head development.","method":"RNA binding assay (in vitro), morpholino knockdown, genetic rescue with wnt8a morpholino, microarray","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro RNA binding assay plus genetic epistasis (wnt8a rescue), single lab","pmids":["24038582"],"is_preprint":false},{"year":2013,"finding":"RNA immunoprecipitation in mouse ES cells showed that Rbm47 binds to the Nanog transcript but does not bind Sox2 or Oct4 transcripts.","method":"HA-tagged RBM47 overexpression, RNA-binding protein immunoprecipitation (RIP), RT-PCR","journal":"Molecular biology reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/RIP experiment, single lab, limited mechanistic follow-up","pmids":["23649762"],"is_preprint":false},{"year":2016,"finding":"Rbm47 function is required in the embryo proper (not the visceral endoderm) for viability and growth; conditional tissue-specific inactivation using Cre/FLP recombinase on a FlEx gene-trap cassette showed Rbm47gt/gt mutants die at mid-gestation.","method":"Conditional tissue-specific knockout mice (Cre/FLP recombinase system), embryonic lethal phenotyping","journal":"Genesis (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined developmental phenotype and tissue specificity, single lab","pmids":["26789794"],"is_preprint":false},{"year":2022,"finding":"RBM47 stabilizes SNHG5 lncRNA by directly binding to it; SNHG5 in turn inhibits FOXO3 ubiquitination and degradation by recruiting USP21, promoting FOXO3 nuclear translocation and activation of autophagy-related genes (ATG3, ATG5). FOXO3 also activates RBM47 expression, forming a positive feedback loop.","method":"RIP assay, RNA stability assay, co-immunoprecipitation, immunofluorescence (FOXO3 localization), in vitro and in vivo functional assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP for direct RNA binding, Co-IP, localization imaging, multiple pathway validations, single lab","pmids":["35338124"],"is_preprint":false},{"year":2022,"finding":"RBM47 stabilizes UPF1 mRNA by binding its 3'UTR (acting as an RNA-binding protein), and also promotes UPF1 transcription (acting as a transcription factor/DNA-binding protein), thereby suppressing HCC progression.","method":"RNA immunoprecipitation, mRNA stability assay, ChIP/transcriptional reporter, in vitro and xenograft in vivo assays","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP and mRNA stability plus transcriptional assay, single lab, two orthogonal mechanisms","pmids":["35831298"],"is_preprint":false},{"year":2023,"finding":"RBM47 undergoes ISGylation at lysine 329 in a phosphorylation-dependent manner (S309 phosphorylation primes ISGylation); RBM47-ISGylation regulates TSC22D3 mRNA expression, and K329R knockin mice lacking RBM47-ISGylation show impaired immune activation and increased susceptibility to lung injury and tumorigenesis.","method":"K329R knockin mouse model, nanobody-targeted E3 ligase for site-specific ISGylation, RNA-seq, functional immune assays","journal":"Cell death discovery","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — knockin mouse with defined mutation, mechanistic epistasis, multiple orthogonal readouts including site-specific ISGylation in human cells","pmids":["38036512"],"is_preprint":false},{"year":2024,"finding":"OTUD4 directly interacts with RBM47 and promotes its stability via deubiquitination; stabilized RBM47 then enhances ATF3 mRNA stability, promoting ATF3-mediated ferroptosis in clear cell renal cell carcinoma.","method":"Co-immunoprecipitation (OTUD4-RBM47 interaction), deubiquitination assay, mRNA stability assay, rescue experiments","journal":"Apoptosis","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP plus deubiquitination assay plus mRNA stability, rescue experiments, single lab","pmids":["38553613"],"is_preprint":false},{"year":2021,"finding":"RBM47 knockdown in mESCs perturbs primitive endoderm marker expression and increases GATA4+ PrE-like cells; this misregulation is reversed by FGFR or MEK inhibitors, implicating RBM47 in regulating FGF-ERK signaling during differentiation. RBM47 is also required for proper neuroectodermal and endodermal differentiation.","method":"siRNA knockdown in mouse ESCs, FGFR/MEK inhibitor rescue, lineage-specific differentiation assays, teratoma assays","journal":"Stem cell reviews and reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KD with pharmacological epistasis rescue, multiple differentiation readouts, single lab","pmids":["35986129"],"is_preprint":false},{"year":2023,"finding":"RBM47 binds to flanking introns of circFNDC3B pre-mRNA to facilitate its biogenesis, resulting in reduced linear FNDC3B mRNA levels and a circFNDC3B/FNDC3B mRNA imbalance in osteosarcoma.","method":"RIP assay, RNA-FISH, RNA stability analysis, functional assays","journal":"Cancer cell international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single RIP assay, single lab, limited mechanistic follow-up for this specific interaction","pmids":["38129874"],"is_preprint":false},{"year":2024,"finding":"RBM47 stabilizes inflammatory gene mRNAs and activates the NF-κB pathway to promote M2 macrophage polarization in GBM; NF-κB in turn acts as a transcription factor to enhance RBM47 transcriptional activity, forming a positive feedback loop. RIP and CHIP assays confirmed these interactions.","method":"RNA-seq, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP), immunofluorescence, in vitro and in vivo functional assays","journal":"Phytomedicine","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus ChIP, positive feedback validated by two orthogonal methods, single lab","pmids":["38518642"],"is_preprint":false},{"year":2021,"finding":"RBM47 inhibits K562 cell proliferation by binding HMGA2 mRNA and promoting its degradation, thereby reducing HMGA2 protein expression; overexpression of RBM47 decreases HMGA2 expression and inhibits cell cycle progression.","method":"RNA immunoprecipitation (RIP), mRNA stability assay (RT-qPCR with actinomycin D), Western blot, CCK-8/flow cytometry","journal":"Zhongguo shi yan xue ye xue za zhi","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single RIP assay plus mRNA stability, single lab, limited independent validation","pmids":["34105460"],"is_preprint":false},{"year":2022,"finding":"RBM47 binds to PTEN mRNA and stabilizes it, thereby suppressing PI3K/AKT signaling in colorectal cancer; miR-181c/d-5p directly targets RBM47 to downregulate it and reactivate PI3K/AKT signaling.","method":"RNA pulldown, luciferase reporter assay, RNA immunoprecipitation (RIP), mRNA stability assay, rescue experiments","journal":"Molecular carcinogenesis","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RNA pulldown, luciferase, and RIP for direct binding plus functional rescue, single lab","pmids":["36321407"],"is_preprint":false},{"year":2025,"finding":"RBM47 directly binds the 3'UTR of cGAS mRNA via its RRM2 domain to enhance cGAS mRNA stability, thereby promoting cGAS-STING signaling and neuronal ferroptosis in a microglial context; RUNX1 directly binds the Rbm47 promoter to facilitate its transcription.","method":"RIP assay (RRM2 domain), promoter binding (ChIP implied), cGAS inhibitor epistasis, KD/OE functional assays in cells and mice","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — domain-specific RIP, pharmacological epistasis, in vivo KD/OE, single lab","pmids":["41407921"],"is_preprint":false},{"year":2025,"finding":"RBM47 binds the 3'UTR of GSDMA mRNA and stabilizes it; ectopic RBM47 increases GSDMA mRNA and protein, while RBM47 knockdown reduces GSDMA. GSDMA is necessary for RBM47-induced mesenchymal-to-epithelial transition (MET), suppression of migration/invasion, and pyroptosis in colorectal cancer cells.","method":"RNA-Seq, RIP assay (direct 3'UTR binding), mRNA stability, GSDMA rescue/knockdown epistasis, MET and pyroptosis functional assays","journal":"Cancers","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP plus mRNA stability plus genetic epistasis (GSDMA KD rescue), multiple functional readouts, single lab","pmids":["41681975"],"is_preprint":false},{"year":2025,"finding":"RBM47 was identified as the trans-acting splicing factor that regulates tissue-specific alternative splicing of SEC31A (inclusion of a specific exon in digestive tissues); RBM47-regulated SEC31A splicing controls lipid transport (secretion of large cargo). Correlation of SEC31A alternative splicing with RBM47 expression across tissues was validated experimentally.","method":"RNA-seq across human tissues, in silico correlation of splicing with RBP expression, experimental validation of RBM47-mediated SEC31A splicing, lipid transport functional assay","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — bioinformatic identification plus experimental validation of RBM47-mediated splicing and functional consequence, single study","pmids":["40436629"],"is_preprint":false},{"year":2025,"finding":"RBM47 stabilizes NEDD4L mRNA by binding to it, leading to increased NEDD4L-mediated ubiquitination and degradation of TRAF2, thereby promoting cellular injury and atherosclerotic plaque instability; silencing RBM47 reduced NEDD4L expression and attenuated TRAF2 ubiquitination.","method":"RIP assay, mRNA stability assay, NEDD4L-TRAF2 interaction confirmation, functional plaque stability assays in murine and cellular AS models","journal":"International immunopharmacology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, limited detail in abstract on method rigor, no independent replication","pmids":["42177907"],"is_preprint":false},{"year":2025,"finding":"HDAC2 promotes RBM47 expression through H3K27 deacetylation; RBM47 overexpression increases NONO expression in medulloblastoma cells, defining a HDAC2/RBM47/NONO axis in MB tumorigenesis.","method":"ChIP-qPCR, luciferase reporter assay, qRT-PCR, Western blot, KD functional assays","journal":"Translational oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ChIP-qPCR and luciferase for epigenetic regulation, but NONO linkage to RBM47 lacks direct binding evidence, single lab","pmids":["41027284"],"is_preprint":false},{"year":2025,"finding":"RBM47 destabilizes ITGAV (integrin αV) mRNA by binding to AU-rich elements in its 3'UTR; miR-122 suppresses RBM47 expression, thereby elevating ITGAV, which activates latent TGF-β and promotes TGF-β signaling and HCC cell metastasis.","method":"Luciferase reporter, RIP assay (RBM47-ITGAV 3'UTR), mRNA stability assay, functional migration/invasion and in vivo pulmonary metastasis assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP and luciferase for direct binding, mRNA stability, in vivo metastasis model, single lab","pmids":["40638600"],"is_preprint":false},{"year":2026,"finding":"RBM47 enhances ENC1 mRNA stability by binding to AU-rich elements in ENC1 mRNA, thereby curbing NRF2 synthesis and nuclear translocation in macrophages during atherosclerosis.","method":"RIP assay (AU-rich element binding), mRNA stability assay, macrophage-specific AAV-mediated knockdown in vivo, ENC1/RBM47 rescue experiments","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP for direct binding plus in vivo AAV knockdown, rescue experiments, single lab","pmids":["41962778"],"is_preprint":false},{"year":2025,"finding":"METTL3/YTHDF1-dependent m6A methylation decreases RBM47 expression in NSCLC; RBM47 destabilizes PD-L1 mRNA via binding its 3'UTR, thereby enhancing T-cell-mediated antitumor activity.","method":"Methylated RIP-PCR (m6A modification), RIP assay (PD-L1 3'UTR binding), functional T-cell cytotoxicity assays, in vitro and in vivo cancer stem cell assays","journal":"Journal of thoracic disease","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, RIP assay for PD-L1 binding with functional readout but limited mechanistic depth for m6A regulation","pmids":["41376900"],"is_preprint":false},{"year":2023,"finding":"RBM47 binds to and stabilizes FBXO2 mRNA, promoting phosphorylation of STAT3 in chondrocytes, thereby advancing osteoarthritis development; RBM47 knockdown alleviates inflammation, apoptosis, and ECM degradation in IL-1β-treated chondrocytes.","method":"RIP assay, mRNA stability assay, STAT3 phosphorylation Western blot, FBXO2/STAT3 rescue experiments, in vitro chondrocyte model","journal":"Biochemical genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — RIP and mRNA stability assay, single lab, limited mechanistic depth linking FBXO2 to STAT3","pmids":["38070024"],"is_preprint":false},{"year":2026,"finding":"CCDC12 knockdown leads to increased exon 5 skipping in RBM47 pre-mRNA, producing a truncated RBM47 isoform with reduced tumor-suppressive activity; reintroduction of full-length RBM47 partially restores impaired cellular phenotypes in breast cancer.","method":"Transcriptomic analysis, splicing assays, RBM47 full-length rescue experiments, functional proliferation/metastasis assays","journal":"International journal of biological macromolecules","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, splicing and rescue assays without detailed mechanistic follow-up of the CCDC12-RBM47 splicing interaction","pmids":["41690343"],"is_preprint":false},{"year":2025,"finding":"FOXA1 directly binds FOXA1 binding sites within the RBM47 promoter region to activate RBM47 transcription; RBM47 upregulation is necessary for FOXA1-mediated mesenchymal-to-epithelial transition and inhibition of CRC cell migration. RBM47 promoter CpG methylation silences RBM47 in mesenchymal-like CRC cells.","method":"ChIP (FOXA1 binding to RBM47 promoter), ectopic FOXA1 expression, RBM47 rescue experiments, bisulfite sequencing/methylation analysis","journal":"Molecular biomedicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for direct promoter binding, genetic rescue epistasis, methylation analysis, single lab with multiple orthogonal methods","pmids":["41335176"],"is_preprint":false},{"year":2023,"finding":"Intestine-specific Rbm47 knockout mice exhibit increased proliferation and abnormal villus morphology; these mice show upregulation of antioxidant, Wnt signaling pathways, stem cell and developmental genes, are protected against colitis but develop spontaneous polyposis with age; Rbm47-IKO ApcMin/+ mice show increased polyp burden. Alternative splicing of TJP1 mRNA is altered in human CRC consistent with loss of RBM47.","method":"Intestine-specific conditional knockout mice (Rbm47-IKO), organoid assays, radiation/chemical colitis models, ApcMin/+ cross, RNA-seq for splicing and expression changes","journal":"JCI insight","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean tissue-specific KO, multiple in vivo models (colitis, tumorigenesis, polyposis), multiple orthogonal phenotypic and molecular readouts","pmids":["37014710"],"is_preprint":false},{"year":2024,"finding":"RBM47 binds the 3'UTR of PDIA6 mRNA and maintains its stability, increasing PDIA6 expression in pancreatic cancer cells; PDIA6 overexpression reverses the suppressive effects of RBM47 knockdown on cell proliferation and immune evasion, establishing RBM47-PDIA6 as a functional axis.","method":"RNA immunoprecipitation (RIP), dual luciferase reporter assay, mRNA stability assay, rescue experiments, xenograft model","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus luciferase plus rescue, single lab, in vivo xenograft","pmids":["39741300"],"is_preprint":false},{"year":2025,"finding":"RBM47 directly interacts with HOXB-AS1 lncRNA, interfering with the HOXB-AS1–p53 protein interaction; this promotes p53 nuclear entry and activation of p53 signaling in renal cell carcinoma cells.","method":"Co-immunoprecipitation (RBM47-HOXB-AS1 interaction), p53 nuclear localization assay, functional knockdown/rescue experiments","journal":"Cell death discovery","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP/RIP for interaction, single lab, mechanism of displacing p53 from lncRNA based on limited evidence in abstract","pmids":["37660095"],"is_preprint":false}],"current_model":"RBM47 is a multi-domain RNA-binding protein (three RRM domains) that operates as a broadly acting post-transcriptional regulator: it serves as the primary cofactor for APOBEC1-mediated C-to-U RNA editing (replacing A1CF in vivo), stabilizes or destabilizes specific target mRNAs by binding their 3'UTR AU-rich or (U)GCAUG elements, and regulates alternative splicing (including of TJP1 and SEC31A) through its first RRM domain; additionally, RBM47 regulates transcription of p53, BCAT1, and UPF1 by binding their promoters, is itself subject to ISGylation at K329 (primed by S309 phosphorylation) and deubiquitination by OTUD4, and is transcriptionally controlled by FOXA1, RUNX1, and HDAC2/H3K27 deacetylation. Through these combined RNA-level and transcriptional activities, RBM47 suppresses Wnt/β-catenin signaling, modulates interferon and innate immune responses (stabilizing IFNAR1 mRNA), controls the p53–p21 cell fate axis, and functions as a context-dependent tumor suppressor or oncogene in diverse cancer types."},"narrative":{"mechanistic_narrative":"RBM47 is a multi-domain RNA-binding protein that acts as a broadly-acting post-transcriptional regulator, governing mRNA editing, stability, and splicing across diverse tissues and disease contexts [PMID:24898756, PMID:24916387]. It is the essential cofactor for APOBEC1-mediated C-to-U RNA editing, physically interacting with APOBEC1 and substituting for A1CF; intestine- and liver-specific Rbm47 knockouts abolish or reduce apoB and other target editing, while RBM47/A1CF act both independently and in tissue-specific combination to dictate editing site selection [PMID:24916387, PMID:30309881, PMID:30844405]. Through its RRM domains, RBM47 recognizes (U)GCAUG and AU-rich elements to control alternative splicing — promoting TJP1 exon-20 inclusion via its first RRM to restrain cell migration, and directing tissue-specific SEC31A splicing that governs large lipid-cargo secretion [PMID:31358901, PMID:40436629]. The dominant theme across its targets is sequence-specific binding to 3'UTRs that stabilizes (or, for select transcripts, destabilizes) mRNAs: it stabilizes IFNAR1 to amplify interferon-stimulated antiviral responses [PMID:34160127], stabilizes Wnt-pathway and growth-suppressive transcripts including DKK1 and AXIN1 [PMID:24898756, PMID:32891348], and destabilizes pro-tumorigenic transcripts such as ITGAV and PD-L1 [PMID:40638600, PMID:41376900]. RBM47 additionally functions at the promoter level, controlling transcription of p53 — thereby setting the p53–p21 cell-fate switch after DNA damage — and of UPF1 [PMID:31511650, PMID:35831298]. RBM47 itself is regulated by ISGylation at K329 (primed by S309 phosphorylation), which tunes immune activation and tumor susceptibility, by OTUD4-mediated deubiquitination that stabilizes the protein, and transcriptionally by FOXA1, RUNX1, and HDAC2/H3K27 deacetylation [PMID:38036512, PMID:38553613, PMID:41407921, PMID:41335176]. Genetic loss-of-function in mice establishes RBM47 as required for embryonic viability and intestinal homeostasis, where its absence drives aberrant proliferation, altered Wnt signaling, and spontaneous polyposis [PMID:26789794, PMID:37014710]. Through these combined activities RBM47 behaves as a context-dependent tumor suppressor or oncogene.","teleology":[{"year":2013,"claim":"Established that RBM47 is a bona fide RNA-binding (not ssDNA-binding) protein with developmental function, placing it upstream of Wnt8a in head formation.","evidence":"In vitro RNA binding assay and zebrafish morpholino knockdown rescued by wnt8a morpholino","pmids":["24038582"],"confidence":"Medium","gaps":["Direct mRNA targets mediating Wnt8a regulation not identified","Binding specificity/sequence preference undefined at this stage"]},{"year":2014,"claim":"Defined RBM47's transcriptome-wide binding landscape and a concrete tumor-suppressive mechanism, answering how it engages mRNAs to alter splicing and abundance.","evidence":"HITS-CLIP, mRNA stability assays, breast cancer models","pmids":["24898756"],"confidence":"High","gaps":["Full set of functionally relevant targets beyond DKK1 not resolved","Determinants of stabilize-vs-destabilize outcome unclear"]},{"year":2014,"claim":"Identified RBM47 as a genuine APOBEC1 editing cofactor capable of replacing A1CF, redefining the in vivo machinery for C-to-U RNA editing.","evidence":"Co-IP, in vitro editing reconstitution, Rbm47 mutant mice","pmids":["24916387"],"confidence":"High","gaps":["Structural basis of APOBEC1 engagement not determined","Relative in vivo contribution of RBM47 vs A1CF per tissue not yet quantified"]},{"year":2016,"claim":"Showed RBM47 is required cell-autonomously in the embryo proper for viability, establishing an essential developmental role.","evidence":"Conditional Cre/FLP gene-trap knockout mice with mid-gestation lethality","pmids":["26789794"],"confidence":"Medium","gaps":["Molecular targets responsible for lethality not identified","Affected tissue/lineage not pinpointed"]},{"year":2018,"claim":"Resolved the tissue-specific division of labor between RBM47 and A1CF in dictating APOBEC1 editing site selection.","evidence":"Liver- and intestine-specific and double conditional knockout mice with editing quantification","pmids":["30309881"],"confidence":"High","gaps":["Rules governing which sites require RBM47 vs A1CF undefined","Mechanism of cofactor cooperativity not structurally explained"]},{"year":2018,"claim":"Extended RBM47's role to immune regulation, showing AU-rich-element-mediated mRNA stabilization controls cytokine output.","evidence":"RIP, mRNA stability assay, IL-10/Treg functional assays in B cells","pmids":["29844590"],"confidence":"Medium","gaps":["Single lab; physiological relevance in immune disease not tested","Binding specificity within Il10 3'UTR not mapped"]},{"year":2019,"claim":"Mapped a domain-specific splicing function, demonstrating the first RRM mediates (U)GCAUG-directed exon inclusion with migration consequences.","evidence":"Splicing reporters, RRM mutagenesis, migration assays on TJP1","pmids":["31358901"],"confidence":"High","gaps":["Genome-wide splicing program beyond TJP1 incomplete","Cooperating splicing factors not defined here"]},{"year":2019,"claim":"Revealed an unexpected transcriptional role: RBM47 controls p53 promoter activity and thereby the p53-p21 death/senescence switch.","evidence":"siRNA knockdown, overexpression, luciferase promoter assays","pmids":["31511650"],"confidence":"Medium","gaps":["Direct promoter binding vs indirect effect not fully distinguished","DNA-binding mode of RBM47 unresolved"]},{"year":2019,"claim":"Defined the minimal RBM47 domain requirement for editing and differential activity versus A1CF across targets and species.","evidence":"Cell-based fluorescence editing reconstitution with domain truncation in HEK293T","pmids":["30844405"],"confidence":"High","gaps":["Atomic-resolution structure of editing complex absent","Basis of human-mouse activity differences unexplained"]},{"year":2020,"claim":"Consolidated RBM47's Wnt-suppressive role through AXIN1 mRNA stabilization in lung cancer, and revealed a divergent zebrafish role degrading MAVS to limit IFN.","evidence":"RIP, mRNA stability, knockdown tumor models (AXIN1); Co-IP and lysosome inhibitor assays (zebrafish MAVS)","pmids":["32891348","32859727"],"confidence":"Medium","gaps":["Apparent opposing effects on innate immunity across systems unreconciled","Mechanism targeting MAVS to lysosome not molecularly defined"]},{"year":2021,"claim":"Established RBM47 as an interferon-inducible amplifier of antiviral immunity by stabilizing IFNAR1 mRNA, and added BCAT1 promoter and hnRNPM-cooperative splicing roles.","evidence":"Reciprocal RIP, mRNA stability, multiple virus infection models (IFNAR1); ChIP and Co-IP (BCAT1/hnRNPM)","pmids":["34160127","34274258"],"confidence":"High","gaps":["How viral induction of RBM47 is wired upstream not fully defined","Scope of hnRNPM-cooperative splicing targets incomplete"]},{"year":2021,"claim":"Implicated RBM47 in stem-cell differentiation via FGF-ERK signaling and added growth-suppressive HMGA2 mRNA destabilization.","evidence":"ESC knockdown with FGFR/MEK inhibitor rescue, differentiation assays; RIP/mRNA stability for HMGA2","pmids":["35986129","34105460"],"confidence":"Medium","gaps":["Direct RBM47 targets within FGF-ERK axis unidentified","HMGA2 finding (Low) is single RIP without independent validation"]},{"year":2022,"claim":"Demonstrated dual RNA-binding and transcription-factor activity on a single target (UPF1) and broadened the 3'UTR-stabilization repertoire to tumor-suppressive transcripts.","evidence":"RIP, mRNA stability, ChIP/reporter, xenografts (UPF1); RIP and rescue (PTEN, SNHG5/FOXO3)","pmids":["35831298","36321407","35338124"],"confidence":"Medium","gaps":["Distinct DNA- vs RNA-binding determinants not separated","Feedback loop kinetics (FOXO3-RBM47) not quantified"]},{"year":2023,"claim":"Defined post-translational control of RBM47 by phosphorylation-primed ISGylation at K329, linking this modification to immune activation and tumor susceptibility in vivo.","evidence":"K329R knockin mice, site-specific nanobody-directed ISGylation, RNA-seq, immune assays","pmids":["38036512"],"confidence":"High","gaps":["Kinase responsible for S309 priming not identified","How ISGylation alters RBM47 RNA target selection unresolved"]},{"year":2023,"claim":"Provided definitive in vivo evidence for RBM47 as an intestinal tumor suppressor controlling proliferation, Wnt, and colitis-associated polyposis.","evidence":"Intestine-specific knockout mice, organoids, colitis and ApcMin/+ models, RNA-seq","pmids":["37014710"],"confidence":"High","gaps":["Which individual targets drive polyposis not isolated","Mechanism of colitis protection vs tumor promotion duality unclear"]},{"year":2024,"claim":"Identified OTUD4 as a deubiquitinase stabilizing RBM47, coupling protein turnover to ferroptosis regulation via ATF3.","evidence":"Co-IP, deubiquitination assay, mRNA stability, rescue in ccRCC","pmids":["38553613"],"confidence":"Medium","gaps":["E3 ligase opposing OTUD4 not identified","Single lineage context (ccRCC) only"]},{"year":2025,"claim":"Expanded RBM47 target logic to context-dependent destabilization (ITGAV, PD-L1) and stabilization (cGAS, GSDMA, PDIA6, NEDD4L) controlling metastasis, immunity, and cell death.","evidence":"RIP/luciferase/mRNA-stability and in vivo functional assays across multiple cancers; RRM2-specific binding for cGAS","pmids":["40638600","41376900","41407921","41681975","39741300","42177907"],"confidence":"Medium","gaps":["Determinants selecting stabilization vs destabilization across targets undefined","Several of these single-lab findings lack reciprocal validation"]},{"year":2025,"claim":"Clarified upstream transcriptional and splicing control of RBM47 itself, identifying FOXA1, RUNX1, and HDAC2/H3K27 deacetylation as regulators and CpG methylation as a silencing mechanism.","evidence":"ChIP, reporter, bisulfite sequencing, rescue assays (FOXA1, RUNX1, HDAC2)","pmids":["41335176","41407921","41027284"],"confidence":"Medium","gaps":["Hierarchy among these upstream regulators not established","Context dependence of each regulator across tissues unclear"]},{"year":null,"claim":"How RBM47 chooses between mutually exclusive molecular outputs — editing cofactor, mRNA stabilizer, mRNA destabilizer, splicing factor, or promoter-bound transcriptional regulator — on a given transcript remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model integrating RNA, DNA, and APOBEC1 binding","Rules linking post-translational state (ISGylation/ubiquitination) to target selection unknown","Mechanistic basis of context-dependent tumor-suppressor vs oncogene behavior undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,1,3,6,8,11]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[1,2,5]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[4,9,15]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[9,15,33]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4,9,33]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,3]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[6,8,16]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,7,34]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,7,11,22]}],"complexes":["APOBEC1 RNA editing complex (APOBEC1-RBM47)"],"partners":["APOBEC1","A1CF","HNRNPM","OTUD4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A0AV96","full_name":"RNA-binding protein 47","aliases":["RNA-binding motif protein 47"],"length_aa":593,"mass_kda":64.1,"function":"Single-stranded RNA-binding protein that functions in a variety of RNA processes, including alternative splicing, RNA stabilization, and RNA editing (PubMed:24038582, PubMed:24916387, PubMed:27050523, PubMed:30844405, PubMed:31358901, PubMed:34160127). Functions as an enzyme-substrate adapter for the cytidine deaminase APOBEC1. With APOBEC1 forms an mRNA editing complex involved into cytidine to uridine editing of a variety of mRNA molecules (PubMed:24038582, PubMed:24916387, PubMed:30844405). Through the binding of their 3'UTR, also stabilizes a variety of mRNAs and regulates the expression of genes such as the interferon alpha/beta receptor and interleukin-10 (PubMed:34160127). Also involved in the alternative splicing of several genes including TJP1. Binds the pre-mRNA (U)GCAUG consensus sequences in downstream intronic regions of alternative exons, regulating their exclusion and inclusion into mRNAs (PubMed:27050523, PubMed:31358901). Independently of its RNA-binding activity, could negatively regulate MAVS by promoting its lysosomal degradation (By similarity)","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/A0AV96/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RBM47","classification":"Not Classified","n_dependent_lines":30,"n_total_lines":1208,"dependency_fraction":0.024834437086092714},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RBM47","total_profiled":1310},"omim":[{"mim_id":"619104","title":"RNA-BINDING MOTIF PROTEIN 47; RBM47","url":"https://www.omim.org/entry/619104"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RBM47"},"hgnc":{"alias_symbol":["FLJ20273","NET18"],"prev_symbol":[]},"alphafold":{"accession":"A0AV96","domains":[{"cath_id":"3.30.70.330","chopping":"33-147","consensus_level":"high","plddt":90.198,"start":33,"end":147},{"cath_id":"3.30.70.330","chopping":"153-231","consensus_level":"high","plddt":87.2299,"start":153,"end":231},{"cath_id":"3.30.70.330","chopping":"240-321","consensus_level":"high","plddt":89.3737,"start":240,"end":321}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A0AV96","model_url":"https://alphafold.ebi.ac.uk/files/AF-A0AV96-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A0AV96-F1-predicted_aligned_error_v6.png","plddt_mean":63.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RBM47","jax_strain_url":"https://www.jax.org/strain/search?query=RBM47"},"sequence":{"accession":"A0AV96","fasta_url":"https://rest.uniprot.org/uniprotkb/A0AV96.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A0AV96/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A0AV96"}},"corpus_meta":[{"pmid":"24898756","id":"PMC_24898756","title":"Loss 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(most prominently in introns and 3'UTRs) as revealed by transcriptome-wide HITS-CLIP, and alters splicing and abundance of a subset of target mRNAs; one mechanism of tumor suppression involves stabilization of DKK1 mRNA to inhibit Wnt signaling and breast cancer progression.\",\n      \"method\": \"HITS-CLIP (transcriptome-wide), mRNA stability assays, functional breast cancer models\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — transcriptome-wide HITS-CLIP with multiple functional validations in a single rigorous study\",\n      \"pmids\": [\"24898756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RBM47 interacts with APOBEC1 and A1CF, can substitute for A1CF, and is necessary and sufficient for APOBEC1-mediated C-to-U RNA editing in vitro; Rbm47-deficient mice show impaired C-to-U RNA editing.\",\n      \"method\": \"Co-immunoprecipitation, in vitro RNA editing reconstitution assay, Rbm47 mutant mouse model\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution plus genetic loss-of-function in mice, independently consistent with subsequent studies\",\n      \"pmids\": [\"24916387\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In mouse intestine and liver, RBM47 and A1CF function independently yet interact in a tissue-specific manner to regulate APOBEC1-dependent C-to-U RNA editing site selection; intestine-specific Rbm47 knockout nearly eliminates apoB RNA editing (<6%), while liver-specific knockout reduces editing of a subset of targets; double knockout of both A1cf and Rbm47 eliminates apoB RNA editing in liver.\",\n      \"method\": \"Tissue-specific conditional knockout mice (liver-specific and intestine-specific), RNA editing quantification of multiple targets\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean tissue-specific KO with defined molecular phenotype, replicated across tissues and cofactor combinations\",\n      \"pmids\": [\"30309881\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"RBM47 promotes inclusion of exon 20 (α-domain) of TJP1 pre-mRNA by recognizing (U)GCAUG sequences in the downstream intronic region; the first RRM domain of RBM47 is critical for this alternative splicing regulation. Loss of RBM47-mediated inclusion yields a TJP1-α− isoform that enhances actin stress fiber assembly and promotes cell migration.\",\n      \"method\": \"Splicing reporter assays, RRM domain mutagenesis, RNA binding assays, wound healing/migration assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mutagenesis of RRM domain, direct RNA binding, functional migration readout in single rigorous study\",\n      \"pmids\": [\"31358901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"RBM47 regulates p53 at the transcriptional level: RBM47 knockdown reduces p53 mRNA and protein by impairing p53 promoter activity, and RBM47 overexpression enhances p53 promoter activity. By controlling p53, RBM47 concomitantly controls p21WAF1/CIP1 expression at the transcriptional level, acting as a molecular switch between cell death and senescence after DNA damage.\",\n      \"method\": \"siRNA knockdown, Flag-RBM47 overexpression, luciferase promoter activity assays, Western blot, RT-PCR\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter activity assays with OE and KD, single lab, two orthogonal methods\",\n      \"pmids\": [\"31511650\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"APOBEC1-RBM47 and APOBEC1-A1CF complexes reconstituted in HEK293T cells show differential RNA editing activity across multiple target RNAs; the minimal domain requirement of RBM47 for editing activity was determined, and clear species differences (mouse vs. human) were observed.\",\n      \"method\": \"Cell-based fluorescence RNA editing assay (eGFP subcellular localization), domain truncation/mutagenesis, reconstitution in HEK293T cells\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cell-based reconstitution with domain mutagenesis, multiple RNA targets tested, direct biochemical evidence\",\n      \"pmids\": [\"30844405\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"RBM47 promotes IL-10 mRNA stability in B cells by binding to AU-rich elements in the 3'UTR of Il10 mRNA, thereby elevating IL-10 production and enhancing immunosuppressive B cell function including Foxp3+ Treg induction.\",\n      \"method\": \"mRNA microarray, RNA immunoprecipitation (RIP), mRNA stability assay, overexpression functional assays\",\n      \"journal\": \"Cellular & molecular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus mRNA stability assay plus functional readout, single lab\",\n      \"pmids\": [\"29844590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RBM47 binds the AXIN1 mRNA and stabilizes it, thereby enhancing suppression of Wnt/β-catenin signaling in NSCLC cells; lentiviral knockdown of RBM47 reduces AXIN1 levels and promotes proliferation, migration, and invasion.\",\n      \"method\": \"RNA immunoprecipitation, mRNA stability assay, lentiviral knockdown, in vitro and in vivo functional assays\",\n      \"journal\": \"Surgical oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus mRNA stability plus in vivo tumor model, single lab\",\n      \"pmids\": [\"32891348\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM47 binds the 3'UTR of IFNAR1 mRNA, increases its stability, and retards IFNAR1 degradation, thereby enhancing IFN-stimulated gene expression and broad-spectrum antiviral activity; RBM47 expression is induced by viral infection or interferon stimulation and has no noticeable impact on IFN production itself.\",\n      \"method\": \"RNA immunoprecipitation, mRNA stability assay, multiple virus infection models in vitro and in vivo, ISRE reporter assay\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal RNA-IP, mRNA stability, in vitro and in vivo virus models, multiple orthogonal methods\",\n      \"pmids\": [\"34160127\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM47 binds to the promoter of BCAT1 and regulates its transcription in NPC cells; RBM47 also cooperates with hnRNPM (confirmed by co-immunoprecipitation) to regulate alternative splicing of multiple pre-mRNAs.\",\n      \"method\": \"ChIP (chromatin immunoprecipitation), transcriptome analysis, Co-IP with hnRNPM, functional knockdown assays\",\n      \"journal\": \"Journal of genetics and genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — ChIP for promoter binding and Co-IP for hnRNPM interaction, single lab with two orthogonal methods\",\n      \"pmids\": [\"34274258\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Zebrafish RBM47 interacts with MAVS and promotes its lysosome-dependent degradation, changing MAVS cellular localization from cytoplasm to the lysosome region, thereby inhibiting downstream MITA and IRF3/7 activation and suppressing IFN production.\",\n      \"method\": \"Co-immunoprecipitation, subcellular localization assays, lysosome inhibitor experiments, functional IFN reporter assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP, localization with functional consequence, pathway epistasis, single lab\",\n      \"pmids\": [\"32859727\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Human RBM47 specifically binds RNA but not single-stranded DNA; zebrafish rbm47 knockdown causes headless/small head phenotypes rescued by wnt8a morpholino, placing rbm47 function upstream of Wnt8a signaling in head development.\",\n      \"method\": \"RNA binding assay (in vitro), morpholino knockdown, genetic rescue with wnt8a morpholino, microarray\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro RNA binding assay plus genetic epistasis (wnt8a rescue), single lab\",\n      \"pmids\": [\"24038582\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"RNA immunoprecipitation in mouse ES cells showed that Rbm47 binds to the Nanog transcript but does not bind Sox2 or Oct4 transcripts.\",\n      \"method\": \"HA-tagged RBM47 overexpression, RNA-binding protein immunoprecipitation (RIP), RT-PCR\",\n      \"journal\": \"Molecular biology reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/RIP experiment, single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"23649762\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Rbm47 function is required in the embryo proper (not the visceral endoderm) for viability and growth; conditional tissue-specific inactivation using Cre/FLP recombinase on a FlEx gene-trap cassette showed Rbm47gt/gt mutants die at mid-gestation.\",\n      \"method\": \"Conditional tissue-specific knockout mice (Cre/FLP recombinase system), embryonic lethal phenotyping\",\n      \"journal\": \"Genesis (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined developmental phenotype and tissue specificity, single lab\",\n      \"pmids\": [\"26789794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RBM47 stabilizes SNHG5 lncRNA by directly binding to it; SNHG5 in turn inhibits FOXO3 ubiquitination and degradation by recruiting USP21, promoting FOXO3 nuclear translocation and activation of autophagy-related genes (ATG3, ATG5). FOXO3 also activates RBM47 expression, forming a positive feedback loop.\",\n      \"method\": \"RIP assay, RNA stability assay, co-immunoprecipitation, immunofluorescence (FOXO3 localization), in vitro and in vivo functional assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP for direct RNA binding, Co-IP, localization imaging, multiple pathway validations, single lab\",\n      \"pmids\": [\"35338124\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RBM47 stabilizes UPF1 mRNA by binding its 3'UTR (acting as an RNA-binding protein), and also promotes UPF1 transcription (acting as a transcription factor/DNA-binding protein), thereby suppressing HCC progression.\",\n      \"method\": \"RNA immunoprecipitation, mRNA stability assay, ChIP/transcriptional reporter, in vitro and xenograft in vivo assays\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP and mRNA stability plus transcriptional assay, single lab, two orthogonal mechanisms\",\n      \"pmids\": [\"35831298\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBM47 undergoes ISGylation at lysine 329 in a phosphorylation-dependent manner (S309 phosphorylation primes ISGylation); RBM47-ISGylation regulates TSC22D3 mRNA expression, and K329R knockin mice lacking RBM47-ISGylation show impaired immune activation and increased susceptibility to lung injury and tumorigenesis.\",\n      \"method\": \"K329R knockin mouse model, nanobody-targeted E3 ligase for site-specific ISGylation, RNA-seq, functional immune assays\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — knockin mouse with defined mutation, mechanistic epistasis, multiple orthogonal readouts including site-specific ISGylation in human cells\",\n      \"pmids\": [\"38036512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"OTUD4 directly interacts with RBM47 and promotes its stability via deubiquitination; stabilized RBM47 then enhances ATF3 mRNA stability, promoting ATF3-mediated ferroptosis in clear cell renal cell carcinoma.\",\n      \"method\": \"Co-immunoprecipitation (OTUD4-RBM47 interaction), deubiquitination assay, mRNA stability assay, rescue experiments\",\n      \"journal\": \"Apoptosis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP plus deubiquitination assay plus mRNA stability, rescue experiments, single lab\",\n      \"pmids\": [\"38553613\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM47 knockdown in mESCs perturbs primitive endoderm marker expression and increases GATA4+ PrE-like cells; this misregulation is reversed by FGFR or MEK inhibitors, implicating RBM47 in regulating FGF-ERK signaling during differentiation. RBM47 is also required for proper neuroectodermal and endodermal differentiation.\",\n      \"method\": \"siRNA knockdown in mouse ESCs, FGFR/MEK inhibitor rescue, lineage-specific differentiation assays, teratoma assays\",\n      \"journal\": \"Stem cell reviews and reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KD with pharmacological epistasis rescue, multiple differentiation readouts, single lab\",\n      \"pmids\": [\"35986129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBM47 binds to flanking introns of circFNDC3B pre-mRNA to facilitate its biogenesis, resulting in reduced linear FNDC3B mRNA levels and a circFNDC3B/FNDC3B mRNA imbalance in osteosarcoma.\",\n      \"method\": \"RIP assay, RNA-FISH, RNA stability analysis, functional assays\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single RIP assay, single lab, limited mechanistic follow-up for this specific interaction\",\n      \"pmids\": [\"38129874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBM47 stabilizes inflammatory gene mRNAs and activates the NF-κB pathway to promote M2 macrophage polarization in GBM; NF-κB in turn acts as a transcription factor to enhance RBM47 transcriptional activity, forming a positive feedback loop. RIP and CHIP assays confirmed these interactions.\",\n      \"method\": \"RNA-seq, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP), immunofluorescence, in vitro and in vivo functional assays\",\n      \"journal\": \"Phytomedicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus ChIP, positive feedback validated by two orthogonal methods, single lab\",\n      \"pmids\": [\"38518642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM47 inhibits K562 cell proliferation by binding HMGA2 mRNA and promoting its degradation, thereby reducing HMGA2 protein expression; overexpression of RBM47 decreases HMGA2 expression and inhibits cell cycle progression.\",\n      \"method\": \"RNA immunoprecipitation (RIP), mRNA stability assay (RT-qPCR with actinomycin D), Western blot, CCK-8/flow cytometry\",\n      \"journal\": \"Zhongguo shi yan xue ye xue za zhi\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single RIP assay plus mRNA stability, single lab, limited independent validation\",\n      \"pmids\": [\"34105460\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RBM47 binds to PTEN mRNA and stabilizes it, thereby suppressing PI3K/AKT signaling in colorectal cancer; miR-181c/d-5p directly targets RBM47 to downregulate it and reactivate PI3K/AKT signaling.\",\n      \"method\": \"RNA pulldown, luciferase reporter assay, RNA immunoprecipitation (RIP), mRNA stability assay, rescue experiments\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RNA pulldown, luciferase, and RIP for direct binding plus functional rescue, single lab\",\n      \"pmids\": [\"36321407\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM47 directly binds the 3'UTR of cGAS mRNA via its RRM2 domain to enhance cGAS mRNA stability, thereby promoting cGAS-STING signaling and neuronal ferroptosis in a microglial context; RUNX1 directly binds the Rbm47 promoter to facilitate its transcription.\",\n      \"method\": \"RIP assay (RRM2 domain), promoter binding (ChIP implied), cGAS inhibitor epistasis, KD/OE functional assays in cells and mice\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — domain-specific RIP, pharmacological epistasis, in vivo KD/OE, single lab\",\n      \"pmids\": [\"41407921\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM47 binds the 3'UTR of GSDMA mRNA and stabilizes it; ectopic RBM47 increases GSDMA mRNA and protein, while RBM47 knockdown reduces GSDMA. GSDMA is necessary for RBM47-induced mesenchymal-to-epithelial transition (MET), suppression of migration/invasion, and pyroptosis in colorectal cancer cells.\",\n      \"method\": \"RNA-Seq, RIP assay (direct 3'UTR binding), mRNA stability, GSDMA rescue/knockdown epistasis, MET and pyroptosis functional assays\",\n      \"journal\": \"Cancers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP plus mRNA stability plus genetic epistasis (GSDMA KD rescue), multiple functional readouts, single lab\",\n      \"pmids\": [\"41681975\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM47 was identified as the trans-acting splicing factor that regulates tissue-specific alternative splicing of SEC31A (inclusion of a specific exon in digestive tissues); RBM47-regulated SEC31A splicing controls lipid transport (secretion of large cargo). Correlation of SEC31A alternative splicing with RBM47 expression across tissues was validated experimentally.\",\n      \"method\": \"RNA-seq across human tissues, in silico correlation of splicing with RBP expression, experimental validation of RBM47-mediated SEC31A splicing, lipid transport functional assay\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — bioinformatic identification plus experimental validation of RBM47-mediated splicing and functional consequence, single study\",\n      \"pmids\": [\"40436629\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM47 stabilizes NEDD4L mRNA by binding to it, leading to increased NEDD4L-mediated ubiquitination and degradation of TRAF2, thereby promoting cellular injury and atherosclerotic plaque instability; silencing RBM47 reduced NEDD4L expression and attenuated TRAF2 ubiquitination.\",\n      \"method\": \"RIP assay, mRNA stability assay, NEDD4L-TRAF2 interaction confirmation, functional plaque stability assays in murine and cellular AS models\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, limited detail in abstract on method rigor, no independent replication\",\n      \"pmids\": [\"42177907\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HDAC2 promotes RBM47 expression through H3K27 deacetylation; RBM47 overexpression increases NONO expression in medulloblastoma cells, defining a HDAC2/RBM47/NONO axis in MB tumorigenesis.\",\n      \"method\": \"ChIP-qPCR, luciferase reporter assay, qRT-PCR, Western blot, KD functional assays\",\n      \"journal\": \"Translational oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ChIP-qPCR and luciferase for epigenetic regulation, but NONO linkage to RBM47 lacks direct binding evidence, single lab\",\n      \"pmids\": [\"41027284\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM47 destabilizes ITGAV (integrin αV) mRNA by binding to AU-rich elements in its 3'UTR; miR-122 suppresses RBM47 expression, thereby elevating ITGAV, which activates latent TGF-β and promotes TGF-β signaling and HCC cell metastasis.\",\n      \"method\": \"Luciferase reporter, RIP assay (RBM47-ITGAV 3'UTR), mRNA stability assay, functional migration/invasion and in vivo pulmonary metastasis assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP and luciferase for direct binding, mRNA stability, in vivo metastasis model, single lab\",\n      \"pmids\": [\"40638600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"RBM47 enhances ENC1 mRNA stability by binding to AU-rich elements in ENC1 mRNA, thereby curbing NRF2 synthesis and nuclear translocation in macrophages during atherosclerosis.\",\n      \"method\": \"RIP assay (AU-rich element binding), mRNA stability assay, macrophage-specific AAV-mediated knockdown in vivo, ENC1/RBM47 rescue experiments\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP for direct binding plus in vivo AAV knockdown, rescue experiments, single lab\",\n      \"pmids\": [\"41962778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"METTL3/YTHDF1-dependent m6A methylation decreases RBM47 expression in NSCLC; RBM47 destabilizes PD-L1 mRNA via binding its 3'UTR, thereby enhancing T-cell-mediated antitumor activity.\",\n      \"method\": \"Methylated RIP-PCR (m6A modification), RIP assay (PD-L1 3'UTR binding), functional T-cell cytotoxicity assays, in vitro and in vivo cancer stem cell assays\",\n      \"journal\": \"Journal of thoracic disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, RIP assay for PD-L1 binding with functional readout but limited mechanistic depth for m6A regulation\",\n      \"pmids\": [\"41376900\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RBM47 binds to and stabilizes FBXO2 mRNA, promoting phosphorylation of STAT3 in chondrocytes, thereby advancing osteoarthritis development; RBM47 knockdown alleviates inflammation, apoptosis, and ECM degradation in IL-1β-treated chondrocytes.\",\n      \"method\": \"RIP assay, mRNA stability assay, STAT3 phosphorylation Western blot, FBXO2/STAT3 rescue experiments, in vitro chondrocyte model\",\n      \"journal\": \"Biochemical genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — RIP and mRNA stability assay, single lab, limited mechanistic depth linking FBXO2 to STAT3\",\n      \"pmids\": [\"38070024\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CCDC12 knockdown leads to increased exon 5 skipping in RBM47 pre-mRNA, producing a truncated RBM47 isoform with reduced tumor-suppressive activity; reintroduction of full-length RBM47 partially restores impaired cellular phenotypes in breast cancer.\",\n      \"method\": \"Transcriptomic analysis, splicing assays, RBM47 full-length rescue experiments, functional proliferation/metastasis assays\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, splicing and rescue assays without detailed mechanistic follow-up of the CCDC12-RBM47 splicing interaction\",\n      \"pmids\": [\"41690343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FOXA1 directly binds FOXA1 binding sites within the RBM47 promoter region to activate RBM47 transcription; RBM47 upregulation is necessary for FOXA1-mediated mesenchymal-to-epithelial transition and inhibition of CRC cell migration. RBM47 promoter CpG methylation silences RBM47 in mesenchymal-like CRC cells.\",\n      \"method\": \"ChIP (FOXA1 binding to RBM47 promoter), ectopic FOXA1 expression, RBM47 rescue experiments, bisulfite sequencing/methylation analysis\",\n      \"journal\": \"Molecular biomedicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for direct promoter binding, genetic rescue epistasis, methylation analysis, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"41335176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Intestine-specific Rbm47 knockout mice exhibit increased proliferation and abnormal villus morphology; these mice show upregulation of antioxidant, Wnt signaling pathways, stem cell and developmental genes, are protected against colitis but develop spontaneous polyposis with age; Rbm47-IKO ApcMin/+ mice show increased polyp burden. Alternative splicing of TJP1 mRNA is altered in human CRC consistent with loss of RBM47.\",\n      \"method\": \"Intestine-specific conditional knockout mice (Rbm47-IKO), organoid assays, radiation/chemical colitis models, ApcMin/+ cross, RNA-seq for splicing and expression changes\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean tissue-specific KO, multiple in vivo models (colitis, tumorigenesis, polyposis), multiple orthogonal phenotypic and molecular readouts\",\n      \"pmids\": [\"37014710\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBM47 binds the 3'UTR of PDIA6 mRNA and maintains its stability, increasing PDIA6 expression in pancreatic cancer cells; PDIA6 overexpression reverses the suppressive effects of RBM47 knockdown on cell proliferation and immune evasion, establishing RBM47-PDIA6 as a functional axis.\",\n      \"method\": \"RNA immunoprecipitation (RIP), dual luciferase reporter assay, mRNA stability assay, rescue experiments, xenograft model\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus luciferase plus rescue, single lab, in vivo xenograft\",\n      \"pmids\": [\"39741300\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM47 directly interacts with HOXB-AS1 lncRNA, interfering with the HOXB-AS1–p53 protein interaction; this promotes p53 nuclear entry and activation of p53 signaling in renal cell carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation (RBM47-HOXB-AS1 interaction), p53 nuclear localization assay, functional knockdown/rescue experiments\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP/RIP for interaction, single lab, mechanism of displacing p53 from lncRNA based on limited evidence in abstract\",\n      \"pmids\": [\"37660095\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RBM47 is a multi-domain RNA-binding protein (three RRM domains) that operates as a broadly acting post-transcriptional regulator: it serves as the primary cofactor for APOBEC1-mediated C-to-U RNA editing (replacing A1CF in vivo), stabilizes or destabilizes specific target mRNAs by binding their 3'UTR AU-rich or (U)GCAUG elements, and regulates alternative splicing (including of TJP1 and SEC31A) through its first RRM domain; additionally, RBM47 regulates transcription of p53, BCAT1, and UPF1 by binding their promoters, is itself subject to ISGylation at K329 (primed by S309 phosphorylation) and deubiquitination by OTUD4, and is transcriptionally controlled by FOXA1, RUNX1, and HDAC2/H3K27 deacetylation. Through these combined RNA-level and transcriptional activities, RBM47 suppresses Wnt/β-catenin signaling, modulates interferon and innate immune responses (stabilizing IFNAR1 mRNA), controls the p53–p21 cell fate axis, and functions as a context-dependent tumor suppressor or oncogene in diverse cancer types.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RBM47 is a multi-domain RNA-binding protein that acts as a broadly-acting post-transcriptional regulator, governing mRNA editing, stability, and splicing across diverse tissues and disease contexts [#0, #1]. It is the essential cofactor for APOBEC1-mediated C-to-U RNA editing, physically interacting with APOBEC1 and substituting for A1CF; intestine- and liver-specific Rbm47 knockouts abolish or reduce apoB and other target editing, while RBM47/A1CF act both independently and in tissue-specific combination to dictate editing site selection [#1, #2, #5]. Through its RRM domains, RBM47 recognizes (U)GCAUG and AU-rich elements to control alternative splicing — promoting TJP1 exon-20 inclusion via its first RRM to restrain cell migration, and directing tissue-specific SEC31A splicing that governs large lipid-cargo secretion [#3, #25]. The dominant theme across its targets is sequence-specific binding to 3'UTRs that stabilizes (or, for select transcripts, destabilizes) mRNAs: it stabilizes IFNAR1 to amplify interferon-stimulated antiviral responses [#8], stabilizes Wnt-pathway and growth-suppressive transcripts including DKK1 and AXIN1 [#0, #7], and destabilizes pro-tumorigenic transcripts such as ITGAV and PD-L1 [#28, #30]. RBM47 additionally functions at the promoter level, controlling transcription of p53 — thereby setting the p53–p21 cell-fate switch after DNA damage — and of UPF1 [#4, #15]. RBM47 itself is regulated by ISGylation at K329 (primed by S309 phosphorylation), which tunes immune activation and tumor susceptibility, by OTUD4-mediated deubiquitination that stabilizes the protein, and transcriptionally by FOXA1, RUNX1, and HDAC2/H3K27 deacetylation [#16, #17, #23, #33]. Genetic loss-of-function in mice establishes RBM47 as required for embryonic viability and intestinal homeostasis, where its absence drives aberrant proliferation, altered Wnt signaling, and spontaneous polyposis [#13, #34]. Through these combined activities RBM47 behaves as a context-dependent tumor suppressor or oncogene.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that RBM47 is a bona fide RNA-binding (not ssDNA-binding) protein with developmental function, placing it upstream of Wnt8a in head formation.\",\n      \"evidence\": \"In vitro RNA binding assay and zebrafish morpholino knockdown rescued by wnt8a morpholino\",\n      \"pmids\": [\"24038582\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct mRNA targets mediating Wnt8a regulation not identified\", \"Binding specificity/sequence preference undefined at this stage\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined RBM47's transcriptome-wide binding landscape and a concrete tumor-suppressive mechanism, answering how it engages mRNAs to alter splicing and abundance.\",\n      \"evidence\": \"HITS-CLIP, mRNA stability assays, breast cancer models\",\n      \"pmids\": [\"24898756\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full set of functionally relevant targets beyond DKK1 not resolved\", \"Determinants of stabilize-vs-destabilize outcome unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified RBM47 as a genuine APOBEC1 editing cofactor capable of replacing A1CF, redefining the in vivo machinery for C-to-U RNA editing.\",\n      \"evidence\": \"Co-IP, in vitro editing reconstitution, Rbm47 mutant mice\",\n      \"pmids\": [\"24916387\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of APOBEC1 engagement not determined\", \"Relative in vivo contribution of RBM47 vs A1CF per tissue not yet quantified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed RBM47 is required cell-autonomously in the embryo proper for viability, establishing an essential developmental role.\",\n      \"evidence\": \"Conditional Cre/FLP gene-trap knockout mice with mid-gestation lethality\",\n      \"pmids\": [\"26789794\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular targets responsible for lethality not identified\", \"Affected tissue/lineage not pinpointed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved the tissue-specific division of labor between RBM47 and A1CF in dictating APOBEC1 editing site selection.\",\n      \"evidence\": \"Liver- and intestine-specific and double conditional knockout mice with editing quantification\",\n      \"pmids\": [\"30309881\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Rules governing which sites require RBM47 vs A1CF undefined\", \"Mechanism of cofactor cooperativity not structurally explained\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended RBM47's role to immune regulation, showing AU-rich-element-mediated mRNA stabilization controls cytokine output.\",\n      \"evidence\": \"RIP, mRNA stability assay, IL-10/Treg functional assays in B cells\",\n      \"pmids\": [\"29844590\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; physiological relevance in immune disease not tested\", \"Binding specificity within Il10 3'UTR not mapped\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Mapped a domain-specific splicing function, demonstrating the first RRM mediates (U)GCAUG-directed exon inclusion with migration consequences.\",\n      \"evidence\": \"Splicing reporters, RRM mutagenesis, migration assays on TJP1\",\n      \"pmids\": [\"31358901\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide splicing program beyond TJP1 incomplete\", \"Cooperating splicing factors not defined here\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed an unexpected transcriptional role: RBM47 controls p53 promoter activity and thereby the p53-p21 death/senescence switch.\",\n      \"evidence\": \"siRNA knockdown, overexpression, luciferase promoter assays\",\n      \"pmids\": [\"31511650\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct promoter binding vs indirect effect not fully distinguished\", \"DNA-binding mode of RBM47 unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the minimal RBM47 domain requirement for editing and differential activity versus A1CF across targets and species.\",\n      \"evidence\": \"Cell-based fluorescence editing reconstitution with domain truncation in HEK293T\",\n      \"pmids\": [\"30844405\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-resolution structure of editing complex absent\", \"Basis of human-mouse activity differences unexplained\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Consolidated RBM47's Wnt-suppressive role through AXIN1 mRNA stabilization in lung cancer, and revealed a divergent zebrafish role degrading MAVS to limit IFN.\",\n      \"evidence\": \"RIP, mRNA stability, knockdown tumor models (AXIN1); Co-IP and lysosome inhibitor assays (zebrafish MAVS)\",\n      \"pmids\": [\"32891348\", \"32859727\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Apparent opposing effects on innate immunity across systems unreconciled\", \"Mechanism targeting MAVS to lysosome not molecularly defined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Established RBM47 as an interferon-inducible amplifier of antiviral immunity by stabilizing IFNAR1 mRNA, and added BCAT1 promoter and hnRNPM-cooperative splicing roles.\",\n      \"evidence\": \"Reciprocal RIP, mRNA stability, multiple virus infection models (IFNAR1); ChIP and Co-IP (BCAT1/hnRNPM)\",\n      \"pmids\": [\"34160127\", \"34274258\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How viral induction of RBM47 is wired upstream not fully defined\", \"Scope of hnRNPM-cooperative splicing targets incomplete\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Implicated RBM47 in stem-cell differentiation via FGF-ERK signaling and added growth-suppressive HMGA2 mRNA destabilization.\",\n      \"evidence\": \"ESC knockdown with FGFR/MEK inhibitor rescue, differentiation assays; RIP/mRNA stability for HMGA2\",\n      \"pmids\": [\"35986129\", \"34105460\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct RBM47 targets within FGF-ERK axis unidentified\", \"HMGA2 finding (Low) is single RIP without independent validation\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated dual RNA-binding and transcription-factor activity on a single target (UPF1) and broadened the 3'UTR-stabilization repertoire to tumor-suppressive transcripts.\",\n      \"evidence\": \"RIP, mRNA stability, ChIP/reporter, xenografts (UPF1); RIP and rescue (PTEN, SNHG5/FOXO3)\",\n      \"pmids\": [\"35831298\", \"36321407\", \"35338124\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Distinct DNA- vs RNA-binding determinants not separated\", \"Feedback loop kinetics (FOXO3-RBM47) not quantified\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined post-translational control of RBM47 by phosphorylation-primed ISGylation at K329, linking this modification to immune activation and tumor susceptibility in vivo.\",\n      \"evidence\": \"K329R knockin mice, site-specific nanobody-directed ISGylation, RNA-seq, immune assays\",\n      \"pmids\": [\"38036512\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for S309 priming not identified\", \"How ISGylation alters RBM47 RNA target selection unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Provided definitive in vivo evidence for RBM47 as an intestinal tumor suppressor controlling proliferation, Wnt, and colitis-associated polyposis.\",\n      \"evidence\": \"Intestine-specific knockout mice, organoids, colitis and ApcMin/+ models, RNA-seq\",\n      \"pmids\": [\"37014710\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which individual targets drive polyposis not isolated\", \"Mechanism of colitis protection vs tumor promotion duality unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified OTUD4 as a deubiquitinase stabilizing RBM47, coupling protein turnover to ferroptosis regulation via ATF3.\",\n      \"evidence\": \"Co-IP, deubiquitination assay, mRNA stability, rescue in ccRCC\",\n      \"pmids\": [\"38553613\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 ligase opposing OTUD4 not identified\", \"Single lineage context (ccRCC) only\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Expanded RBM47 target logic to context-dependent destabilization (ITGAV, PD-L1) and stabilization (cGAS, GSDMA, PDIA6, NEDD4L) controlling metastasis, immunity, and cell death.\",\n      \"evidence\": \"RIP/luciferase/mRNA-stability and in vivo functional assays across multiple cancers; RRM2-specific binding for cGAS\",\n      \"pmids\": [\"40638600\", \"41376900\", \"41407921\", \"41681975\", \"39741300\", \"42177907\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Determinants selecting stabilization vs destabilization across targets undefined\", \"Several of these single-lab findings lack reciprocal validation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Clarified upstream transcriptional and splicing control of RBM47 itself, identifying FOXA1, RUNX1, and HDAC2/H3K27 deacetylation as regulators and CpG methylation as a silencing mechanism.\",\n      \"evidence\": \"ChIP, reporter, bisulfite sequencing, rescue assays (FOXA1, RUNX1, HDAC2)\",\n      \"pmids\": [\"41335176\", \"41407921\", \"41027284\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Hierarchy among these upstream regulators not established\", \"Context dependence of each regulator across tissues unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RBM47 chooses between mutually exclusive molecular outputs — editing cofactor, mRNA stabilizer, mRNA destabilizer, splicing factor, or promoter-bound transcriptional regulator — on a given transcript remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model integrating RNA, DNA, and APOBEC1 binding\", \"Rules linking post-translational state (ISGylation/ubiquitination) to target selection unknown\", \"Mechanistic basis of context-dependent tumor-suppressor vs oncogene behavior undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 3, 6, 8, 11]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [1, 2, 5]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [4, 9, 15]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [9, 15, 33]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4, 9, 33]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [6, 8, 16]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 7, 34]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 7, 11, 22]}\n    ],\n    \"complexes\": [\"APOBEC1 RNA editing complex (APOBEC1-RBM47)\"],\n    \"partners\": [\"APOBEC1\", \"A1CF\", \"hnRNPM\", \"OTUD4\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}