{"gene":"RBM24","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2014,"finding":"RBM24 is sufficient to promote muscle-specific exon inclusion in nuclear extracts of non-muscle cells; binding of RBM24 to an intronic splicing enhancer (ISE) is essential and sufficient to overcome repression by an exonic splicing silencer (ESS) containing PTB and hnRNP A1/A2 binding sites. Introduction of ESS and ISE converted a constitutive exon into an RBM24-dependent alternative exon.","method":"In vitro splicing assays in nuclear extracts; recombinant protein; targeted inactivation in mice; exon reporter constructs","journal":"Developmental Cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with recombinant protein, mutagenesis of enhancer/silencer elements, and in vivo mouse knockout with defined phenotypic readout","pmids":["25313962"],"is_preprint":false},{"year":2012,"finding":"Rbm24 loss-of-function in zebrafish causes reduction in sarcomeric proteins, Z-disc abnormality, and diminished heart contractility, establishing a required role for Rbm24 in sarcomere assembly and cardiac function.","method":"Zebrafish loss-of-function; gene expression profiling; protein analysis","journal":"Cardiovascular Research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockdown in vertebrate model with defined sarcomere and contractility phenotype, single lab","pmids":["22345307"],"is_preprint":false},{"year":2013,"finding":"RBM24 binds to the 3'-UTR of p21 transcript via an AU/U-rich element and stabilizes p21 mRNA, increasing p21 half-life and protein levels. The RNA recognition motif (RRM) of RBM24 is required for this binding and p21 upregulation.","method":"mRNA stability assay; RBM24 overexpression/knockdown; RRM domain mutagenesis; RNA binding assay","journal":"Journal of Biological Chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro binding with domain mutagenesis, mRNA half-life measurements, single lab with multiple orthogonal methods","pmids":["24356969"],"is_preprint":false},{"year":2013,"finding":"RBM24 binds to multiple regions in the p63 3'-UTR and destabilizes p63 transcript, decreasing p63 mRNA and protein levels. The 3'-UTR of p63 and the RNA-binding domain of RBM24 are both required for this regulatory interaction.","method":"RBM24 overexpression/knockdown; RNA binding assay; mRNA stability assay; domain deletion analysis","journal":"Molecular Cancer Research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA binding demonstrated, domain requirements defined, single lab with multiple orthogonal methods","pmids":["24375645"],"is_preprint":false},{"year":2018,"finding":"Rbm24, a p53 target gene, regulates p53 mRNA translation by binding to p53 mRNA and interacting with translation initiation factor eIF4E, preventing eIF4E from binding to p53 mRNA and inhibiting assembly of the translation initiation complex. Rbm24-null mice die in utero with endocardial cushion defects partially rescued by p53 deficiency.","method":"Co-immunoprecipitation (RBM24–eIF4E interaction); RNA-binding assay; translation assay; Rbm24/p53 double-knockout mouse rescue","journal":"Cell Death and Differentiation","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP interaction, translation assay, genetic rescue by p53 KO; multiple orthogonal methods in a single rigorous study","pmids":["29358667"],"is_preprint":false},{"year":2009,"finding":"Rbm24 overexpression induces cell cycle arrest and promotes myogenic differentiation in C2C12 cells; knockdown delays differentiation and suppresses cell cycle arrest. Unlike Rbm38 (which binds p21 transcript), the p21-independent pathway of Rbm24 mediates this effect.","method":"RNA interference knockdown; overexpression in C2C12 cells; immunoprecipitation-RT-PCR","journal":"Genes to Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional KD/OE with defined phenotype, single lab; mechanistic pathway partially defined via epistasis with p21","pmids":["19817877"],"is_preprint":false},{"year":2020,"finding":"In zebrafish lens, Rbm24 binds broadly to lens-specific mRNAs via its RRM domain, interacts with cytoplasmic polyadenylation element-binding protein (Cpeb1b) and cytoplasmic poly(A)-binding protein (Pabpc1l) via its C-terminal region, and controls poly(A) tail length of crystallin mRNAs. Loss of Rbm24 shortens poly(A) tails of crystallin mRNAs and reduces their translation, impairing lens transparency.","method":"Zebrafish rbm24 loss-of-function; co-immunoprecipitation; poly(A) tail length assay; RRM domain functional analysis","journal":"Proceedings of the National Academy of Sciences","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP showing Rbm24-Cpeb1b-Pabpc1l complex, poly(A) length assay, domain analysis, and developmental phenotype; multiple orthogonal methods","pmids":["32170011"],"is_preprint":false},{"year":2010,"finding":"Xenopus Seb4/RBM24 expression is directly regulated by MyoD; a 0.65 kb RBM24 regulatory region containing E-boxes is activated by MyoD in reporter assays. Knockdown of Seb4 inhibits myogenic gene expression and myogenesis induced by MyoD.","method":"Hormone-inducible MyoD; RBM24 reporter construct injection; morpholino knockdown in Xenopus","journal":"Mechanisms of Development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay with MyoD E-box, morpholino KD with defined myogenic phenotype, single lab","pmids":["20338237"],"is_preprint":false},{"year":2014,"finding":"Rbm24 protein expression is directly regulated by MyoD in vivo (ChIP assay in chick embryo); Rbm24 accumulates in MyoD-positive myoblasts and is required for somitic myogenic progenitor cells to differentiate into muscle cells.","method":"In vivo chromatin immunoprecipitation (ChIP); morpholino knockdown; immunofluorescence","journal":"Mechanisms of Development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct ChIP evidence for MyoD binding, morpholino KD with differentiation phenotype, single lab","pmids":["25217815"],"is_preprint":false},{"year":2016,"finding":"Rbm24 regulates alternative splicing switch in ESC cardiac lineage differentiation; forced Rbm24 expression in ESCs dramatically induces cardiac specification and switches splicing of pluripotency genes including Tpm1, whose ESC/tissue-specific isoforms are functionally distinct and required for differentiation.","method":"Inducible mouse ESC line; genome-wide RNA-seq; forced expression; functional isoform comparison","journal":"Stem Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide splicing analysis, functional validation of Tpm1 isoforms, single lab","pmids":["26990106"],"is_preprint":false},{"year":2016,"finding":"MicroRNA-222 targets Rbm24 mRNA; downregulation of Rbm24 by miR-222 results in defective exon inclusion in Coro6, Fxr1, and NACA muscle-specific transcripts. Reconstitution of Rbm24 in miR-222-overexpressing cells rescues muscle-specific splicing.","method":"RISC pulldown + RNA-seq; miR-222 overexpression; Rbm24 rescue experiment; splicing assays","journal":"Cell Death & Disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RISC pulldown identifies Rbm24 as miR-222 target, splicing rescue confirms pathway, single lab","pmids":["26844700"],"is_preprint":false},{"year":2016,"finding":"RBM20 and RBM24 cooperatively promote expression of short ENH splice variants by binding the 5' intronic region of exon 11 of the enh gene, which contains an in-phase stop codon.","method":"Co-expression of RBM20 and RBM24; splicing reporter; RNA binding assay","journal":"FEBS Letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding to intronic region demonstrated, cooperative splicing effect shown, single lab","pmids":["27289039"],"is_preprint":false},{"year":2017,"finding":"Stk38 (serine/threonine kinase 38) is an endogenous binding partner of Rbm24 (identified by Co-IP/MS); Stk38 kinase activity-dependently regulates Rbm24 protein stability and phosphorylation in cardiomyocytes. Stk38 knockdown reduces Rbm24 protein levels and impairs sarcomere assembly.","method":"Co-immunoprecipitation coupled with mass spectrometry; kinase inhibitor/activator; Stk38 knockdown; sarcomere analysis","journal":"Scientific Reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP/MS identifies interaction, kinase activity-dependent regulation confirmed with inhibitor/activator, single lab","pmids":["28322254"],"is_preprint":false},{"year":2017,"finding":"RBM24 functions as a cryptic intronic splicing enhancer by binding to an element (IVS20+13-29) downstream of the FD-associated 5' splice site mutation in IKBKAP and promotes U1 snRNP recognition specifically at the mutated (not wild-type) 5' splice site, explaining neuron-specific aberrant splicing in familial dysautonomia.","method":"Mammalian dual-color splicing reporter screen; RBP expression library screen; direct binding assay","journal":"RNA","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional splicing reporter with defined binding element, specificity for mutant vs WT site demonstrated, single lab","pmids":["28592461"],"is_preprint":false},{"year":2018,"finding":"RBM24 interacts with both the 5' and 3' terminal redundancy (TR) sequences of HBV 3.5-kb RNA via its RNA-binding domains. Interaction with 5' TR blocks 80S ribosome assembly on HBV pgRNA, inhibiting core protein translation; interaction with 3' TR enhances HBV RNA stability.","method":"RNA-binding domain interaction assays; 80S ribosome assembly assay; HBV transfection/infection cell model; RBM24 overexpression/knockdown","journal":"Emerging Microbes & Infections","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistically distinct dual functions demonstrated with ribosome assembly assay and RNA stability measurement, single lab","pmids":["29760415"],"is_preprint":false},{"year":2019,"finding":"RBM24 directly binds the lower bulge of the epsilon stem-loop of HBV pgRNA via RNP submotifs, and interacts with HBV polymerase (Pol) in an RNA-independent manner via its alanine-rich domain (ARD) and the Pol reverse transcriptase (RT) domain. RBM24 forms a Pol-RBM24-ε complex that mediates Pol-ε interaction and promotes pgRNA packaging.","method":"Co-immunoprecipitation; RNA binding assays; domain deletion mutants; pgRNA packaging efficiency assay","journal":"Journal of Virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mapping of protein-protein and protein-RNA interactions, functional packaging assay, single lab","pmids":["30626666"],"is_preprint":false},{"year":2020,"finding":"RBM24 protein binds Sox2 mRNA in mouse embryonic eye tissue (RNA immunoprecipitation) and directly binds the Sox2 mRNA 3'-UTR via AU-rich elements (EMSA). RBM24 elevates Sox2 mRNA half-life in an ARE-dependent manner. Loss of Rbm24 downregulates SOX2 and causes microphthalmia/anophthalmia.","method":"RNA immunoprecipitation (RIP) from mouse embryonic tissue; electrophoretic mobility shift assay (EMSA); mRNA half-life assay; CRISPR and morpholino knockdown in mouse and zebrafish","journal":"Human Molecular Genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — RIP in vivo plus EMSA with ARE mutagenesis plus mRNA stability assay plus genetic models in two species; multiple orthogonal methods","pmids":["31814023"],"is_preprint":false},{"year":2018,"finding":"Rbm24 displays cytoplasmic localization in lens, olfactory epithelium, and mechanosensory cells of auditory and vestibular systems during mouse development, consistent with cytoplasmic post-transcriptional regulatory activity in these tissues.","method":"Immunostaining and subcellular localization analysis in mouse embryo sections","journal":"Developmental Dynamics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization data only, no functional consequence directly demonstrated in this study","pmids":["30133047"],"is_preprint":false},{"year":2020,"finding":"During C2C12 myoblast differentiation, Rbm24 undergoes cytoplasm-to-nucleus translocation. In regenerating adult muscle, Rbm24 accumulates in the myonucleus of nascent myofibers. Early in regeneration Rbm24 is required for myogenin expression; late in regeneration it regulates muscle-specific pre-mRNA alternative splicing.","method":"Subcellular fractionation/immunofluorescence during differentiation; satellite cell transplantation; injury-induced regeneration model","journal":"Scientific Reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct subcellular localization with functional consequence (myogenin expression vs. splicing at distinct stages); satellite cell transplantation provides causal evidence; single lab","pmids":["33941806"],"is_preprint":false},{"year":2020,"finding":"Rbm24 conditional knockout in skeletal muscle and satellite cells impairs myogenic fusion and differentiation, delays muscle regeneration after cardiotoxin injury, and dysregulates alternative splicing of Mef2d, Naca, Rock2, and Lrrfip1.","method":"Conditional knockout mice (skeletal muscle-specific and satellite cell-specific); CTX injury model; RNA-seq","journal":"Theranostics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-type-specific KO with defined regeneration phenotype and target splicing events identified, single lab","pmids":["33042276"],"is_preprint":false},{"year":2021,"finding":"RBM24 ablation in hESCs (CRISPR/Cas9) disrupts sarcomere assembly: core myofibrillogenesis proteins (ACTN2, TTN, MYH10) are misspliced, MYH6 cannot replace MYH10, and myofibrillogenesis arrests at the premyofibril stage. RBM24 promotes inclusion of ACTN2 exon 6 (actin-binding domain), and CRISPR deletion of exon 6 or forced expression of full-length ACTN2 in RBM24-/- hESCs confirms exon 6 inclusion is critical for sarcomere assembly.","method":"CRISPR/Cas9 KO in hESCs; transcriptomics; ACTN2 exon 6 CRISPR deletion; forced full-length ACTN2 rescue","journal":"Circulation Research","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO in human cells, specific splicing target identified, exon deletion and rescue experiments converge on mechanism; multiple orthogonal methods","pmids":["34816743"],"is_preprint":false},{"year":2021,"finding":"RBM24 directly binds the GT-rich region (positions 8101-8251) in the 3'-UTR of PTEN mRNA (RIP assay), prolongs PTEN mRNA half-life, and increases PTEN protein levels, suppressing PI3K-Akt signaling. Rbm24-knockout mice develop spontaneous colorectal adenomas with lower PTEN expression.","method":"RNA immunoprecipitation; mRNA stability assay; Rbm24 KO mouse model; APC-min mouse model","journal":"Clinical and Translational Medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP defines binding site, half-life assay confirms stabilization, in vivo KO phenotype; single lab","pmids":["34709758"],"is_preprint":false},{"year":2021,"finding":"RBM24 positively regulates Runx1t1 mRNA stability in bladder cancer cells by directly binding Runx1t1 mRNA; miR-625-5p directly targets and suppresses RBM24 expression; Runx1t1 promotes RBM24 expression via TCF4-mediated suppression of miR-625-5p, forming a positive feedback loop.","method":"RNA immunoprecipitation; luciferase reporter; mRNA stability assay; gain/loss-of-function","journal":"Experimental & Molecular Medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP and luciferase confirm direct binding, feedback loop validated by multiple assays, single lab","pmids":["34021255"],"is_preprint":false},{"year":2022,"finding":"RBM24 ablation in mice and hESC-derived cardiomyocytes causes aberrant shift of CaMKIIδ splicing towards the δ-C isoform, leading to altered Ca2+ handling, prolongation of ventricular action potential and QT interval. CaMKIIδ inhibitor treatment attenuates these electrophysiological abnormalities.","method":"RBM24 knockout mice; hESC-derived cardiomyocyte KD; electrophysiology; CaMKIIδ inhibitor rescue","journal":"Cellular and Molecular Life Sciences","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO mouse and human cell model converge on same splicing event and electrophysiological phenotype; pharmacological rescue confirms mechanism; multiple orthogonal methods","pmids":["36454480"],"is_preprint":false},{"year":2022,"finding":"RBM24 recognizes and binds to the GUGUG element at stem-loop 4 (SL4) in the 5'-UTR of SARS-CoV-2 RNA via its RNP submotifs, prevents 80S ribosome assembly, and inhibits viral polyprotein translation and replication.","method":"RNA binding assay (RNP submotif mapping); 80S ribosome assembly assay; viral replication assay","journal":"Antiviral Research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — specific binding element mapped, ribosome assembly inhibition demonstrated, single lab","pmids":["36464077"],"is_preprint":false},{"year":2022,"finding":"RBM24 regulates mRNA stability of SLC7A11 (a ferroptosis inhibitor); overexpression of RBM24 protects cells from Erastin-induced ferroptosis while knockout sensitizes cells. RBM24 deficiency in mice leads to chronic inflammation and liver steatosis.","method":"RBM24 overexpression/knockout; Erastin-induced ferroptosis assay; SLC7A11 knockdown rescue; lipidomics; mouse model","journal":"Frontiers in Cell and Developmental Biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue (SLC7A11 KD reverses RBM24 effect), in vivo mouse phenotype, single lab","pmids":["36478739"],"is_preprint":false},{"year":2016,"finding":"RBM24 protein binds to MIR143HG RNA, destabilizes its transcript and facilitates its interaction with Ago2 to accelerate MIR143HG degradation. RBM24 also promotes biogenesis of miR-143 (evidenced by siRNA against DROSHA). MIR143HG in turn sponges miR-143 (which targets RBM24 mRNA), forming a negative feedback loop.","method":"RNA binding assay; mRNA stability assay; Ago2 co-immunoprecipitation; DROSHA siRNA; luciferase reporter","journal":"Biochimica et Biophysica Acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein-RNA binding and Ago2 interaction demonstrated, negative feedback loop validated by multiple assays, single lab","pmids":["27565737"],"is_preprint":false},{"year":2017,"finding":"Global RNA immunoprecipitation–microarray (RIP-Chip) profiling of Rbm24 in cardiomyocytes identifies its mRNA binding repertoire. Beyond splicing and mRNA stabilization, Rbm24 destabilizes Chrm2 mRNA via binding a coding-region element, and drives generation of isoforms with alternative transcriptional start sites.","method":"RNA immunoprecipitation coupled to microarray (RIP-Chip); mRNA stability assay; coding-region binding validation","journal":"The International Journal of Biochemistry & Cell Biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide RIP-Chip with follow-up validation of novel Chrm2 coding-region binding and alternative TSS regulation; single lab","pmids":["29104163"],"is_preprint":false},{"year":2016,"finding":"NMR backbone and side-chain resonance assignments of the RRM domain of human RBM24 confirm the canonical RRM domain architecture by secondary chemical shift analysis and relaxation measurements.","method":"NMR spectroscopy (1H, 15N, 13C chemical shift assignments; secondary chemical shift analysis; relaxation measurements)","journal":"Biomolecular NMR Assignments","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — structural characterization of RRM domain by NMR, single paper, no functional mutagenesis in this study","pmids":["27002326"],"is_preprint":false},{"year":2018,"finding":"AAV9-mediated overexpression of Rbm24 in adult mouse heart induces cardiac fibrosis associated with increased TGFβ-signaling genes (TgfβR1, TgfβR2), periostin expression, and fibroblast activation; it also causes splicing changes in PDZ and Lim domain 5, Phospholamban, and Titin, but not in embryonic Rbm24 splicing targets (skNAC, αNAC, Coro6).","method":"AAV9 delivery in adult mice; high-resolution microarrays; histology; gene expression analysis","journal":"Scientific Reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo gain-of-function with genome-wide splicing and expression profiling, single lab","pmids":["30076363"],"is_preprint":false},{"year":2020,"finding":"Rbm24 knockout in mice results in hearing loss and balance deficits; Rbm24 regulates inner-ear-specific alternative splicing including direct regulation of Cdh23 splicing (responsible for Usher syndrome 1D), and loss causes stereocilia integrity defects and hair cell death.","method":"Rbm24 conditional KO mice; auditory testing; RNA-seq splicing analysis; hair cell imaging","journal":"RNA Biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined auditory phenotype, specific splicing target (Cdh23) validated, single lab","pmids":["32887533"],"is_preprint":false},{"year":2020,"finding":"RBM24 is recruited into stress granules under various stress conditions; RBM24 overexpression alone is sufficient to induce stress granule formation. However, knockdown of Rbm24 does not affect stress granule formation.","method":"Immunofluorescence under stress; RBM24 overexpression; Rbm24 knockdown","journal":"Biochemical and Biophysical Research Communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization to SGs shown, induction by OE demonstrated, but functional consequence of SG localization not mechanistically established; single lab","pmids":["35395551"],"is_preprint":false},{"year":2024,"finding":"Psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling; S181 phosphorylation of RBM24 promotes APOE translation. Rbm24 S181A knock-in mice show cardiac contractile dysfunction, atrial fibrillation, dyslipidemia, and sudden death under stress; cardiomyocyte-specific APOE expression rescues cardiac electrophysiological and contractile defects via preventing ROS stress and mitochondrial dysfunction.","method":"Rbm24 S181A knock-in mice; eIF4E2-GSK3β signaling pathway analysis; APOE translation assay; cardiomyocyte-specific APOE rescue; electrophysiology; mitochondria/ROS assays","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — phospho-specific KI mouse model, pathway dissection (eIF4E2-GSK3β), translational target identified (APOE), genetic rescue with APOE; multiple orthogonal methods in a single rigorous study","pmids":["39580475"],"is_preprint":false},{"year":2024,"finding":"POU4F3 directly binds three Rbm24 enhancers in cochlear hair cells (identified by transgenic reporter assays), and Rbm24 expression is completely absent in Pou4f3-null hair cells. GFI1 does not regulate Rbm24 expression. Ectopic Rbm24 alone cannot prevent Pou4f3-null hair cells from degenerating.","method":"In vivo transgenic reporter assay; Pou4f3 and Gfi1 KO mouse analysis; ectopic Rbm24 expression in Pou4f3-KO","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct enhancer binding by POU4F3 identified by in vivo reporter assay with genetic rescue testing, single lab","pmids":["38483314"],"is_preprint":false},{"year":2024,"finding":"RBM24 knockout in mouse brain impairs learning and memory; Rbm24 regulates alternative splicing of synapse-associated genes GluR2 and Prrt1. Rbm24 deletion disrupts excitatory synaptic function and plasticity in hippocampal slices.","method":"Conditional RBM24 KO mice; electrophysiology (hippocampal slices); RNA-seq splicing analysis; behavioral assays","journal":"International Journal of Biological Macromolecules","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined synaptic and behavioral phenotype, specific splicing targets (GluR2, Prrt1) identified; single lab","pmids":["39004256"],"is_preprint":false},{"year":2024,"finding":"Rbm24 maintains Notch1 mRNA stability in adult neural stem/progenitor cells (NSPCs) in the SVZ; Rbm24 deletion impairs NSPC proliferation and neurogenesis in the olfactory bulb. Overexpression of Rbm24 rescues adult neurogenesis and olfactory dysfunction in PD mice, and this rescue is blocked by the Notch1 inhibitor DAPT.","method":"Rbm24 KO mice; Rbm24 overexpression in PD mouse model; DAPT pharmacological inhibition; RNA-seq; immunofluorescence; electrophysiology","journal":"Theranostics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mRNA stability target identified, genetic and pharmacological rescue converge, single lab","pmids":["39113792"],"is_preprint":false},{"year":2025,"finding":"RBM24 stabilizes JAK2 mRNA (via RNA immunoprecipitation and luciferase reporter assays) and promotes JAK2-STAT3-KLF4 signaling to drive VSMC phenotypic switching and vascular remodeling. VSMC-specific Rbm24 KO attenuates neointima formation; AAV-mediated RBM24 overexpression promotes it.","method":"VSMC-specific KO mice; AAV overexpression; mRNA stability assay; RNA immunoprecipitation; luciferase reporter; STAT3 inhibition (shRNA and nifuroxazide)","journal":"Cardiovascular Research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RIP confirms JAK2 mRNA binding, stability assay confirms mechanism, genetic and pharmacological rescue; single lab","pmids":["41216933"],"is_preprint":false},{"year":2025,"finding":"RBM24 directly binds pre-mRNA and facilitates exon inclusion to provide substrate for circ23679 production; RBM24-regulated circRNA production depends on its phosphorylation status. Circ23679 acts as a sponge for miR-15b-5p to inhibit cardiac apoptosis.","method":"circRNA profiling in Rbm24 KO mouse hearts; RBM24 pre-mRNA binding assay; phosphorylation manipulation; circ23679 overexpression in heart failure model","journal":"International Journal of Biological Macromolecules","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct pre-mRNA binding shown, phosphorylation-dependence of circRNA production demonstrated, functional rescue in heart failure model; single lab","pmids":["40250678"],"is_preprint":false},{"year":2026,"finding":"Rbm24 exon 4 is alternatively spliced to produce a short isoform (RBM24-S) that, while sharing the same RRM, binds different mRNA targets affecting their splicing and/or stability compared to RBM24-L. Deletion of exon 4 (abolishing RBM24-S) causes severe hearing loss in both homozygous and heterozygous mice and stereocilia disorganization. Overexpression of RBM24-L in hair cells also causes stereocilia defects and profound hearing loss, demonstrating that proper balance of isoforms is critical.","method":"Exon 4 conditional deletion in mice; RBM24-L overexpression; hearing tests; hair cell imaging; RNA-seq target analysis (Strc)","journal":"Proceedings of the National Academy of Sciences","confidence":"High","confidence_rationale":"Tier 2 / Strong — isoform-specific exon deletion model plus gain-of-function overexpression model converge on stereocilia and hearing phenotype; target mRNA (Strc) identified; multiple orthogonal models","pmids":["41973913"],"is_preprint":false},{"year":2024,"finding":"Rbm24 represses Insm1 expression in cochlear outer hair cells; in Rbm24-null OHCs, Insm1 remains aberrantly expressed and drives OHC death. Simultaneous inactivation of Rbm24 and Insm1 largely rescues OHC survival but only partially restores hair bundle morphology, demonstrating that Rbm24 promotes OHC survival via Insm1 repression independently of its role in hair bundle morphogenesis.","method":"Rbm24-/- mouse; Insm1 overexpression; Rbm24/Insm1 double KO; transcriptomic profiling of purified OHCs","journal":"Development","confidence":"High","confidence_rationale":"Tier 2 / Strong — double KO genetic rescue separates two functions (survival vs. morphogenesis), corroborated by transcriptomics and Insm1 overexpression phenocopy; multiple orthogonal approaches","pmids":["41884985"],"is_preprint":false}],"current_model":"RBM24 is a highly conserved, tissue-restricted RNA-binding protein that acts through its RRM domain to regulate multiple post-transcriptional mechanisms — including pre-mRNA alternative splicing (promoting muscle-, cardiac-, and inner-ear-specific exon inclusion), mRNA stability (stabilizing p21, Sox2, PTEN, Notch1, JAK2; destabilizing p63, Chrm2), cytoplasmic polyadenylation (controlling poly(A) tail length of crystallin mRNAs via interaction with Cpeb1b and Pabpc1l), and translation (inhibiting p53 and viral polyprotein translation by blocking eIF4E or 80S ribosome assembly); its activity and stability are regulated by phosphorylation (Stk38 kinase; GSK3β-mediated S181 phosphorylation linking stress signaling to APOE translation), and it is transcriptionally controlled by MyoD via E-box elements, making it a master post-transcriptional regulator of cardiac and skeletal muscle development, inner ear function, lens differentiation, and neural homeostasis."},"narrative":{"mechanistic_narrative":"RBM24 is a tissue-restricted RNA-binding protein that functions as a master post-transcriptional regulator of striated muscle, inner ear, lens, and neural development through its RRM domain [PMID:25313962, PMID:34816743, PMID:27002326]. In the nucleus it directs tissue-specific alternative splicing: it binds intronic splicing enhancers to overcome silencer-mediated repression and promote muscle-specific exon inclusion [PMID:25313962], and is required for correct splicing of sarcomeric and cardiac transcripts including ACTN2 exon 6 and CaMKIIδ, with loss arresting myofibrillogenesis at the premyofibril stage and prolonging the ventricular action potential [PMID:34816743, PMID:36454480]. RBM24 expression is itself activated by the myogenic transcription factor MyoD via E-box elements, integrating it into the muscle differentiation program where it promotes cell-cycle exit and differentiation [PMID:20338237, PMID:25217815, PMID:19817877]. In the cytoplasm RBM24 controls mRNA fate by sequence-specific binding to AU/U-rich and GT-rich elements: it stabilizes p21, Sox2, PTEN, Notch1 and JAK2 transcripts and destabilizes p63 and Chrm2 [PMID:24356969, PMID:31814023, PMID:34709758, PMID:39113792, PMID:41216933, PMID:24375645, PMID:29104163], and it controls poly(A) tail length of crystallin mRNAs through a complex with Cpeb1b and Pabpc1l to drive lens transparency [PMID:32170011]. It additionally regulates translation, binding p53 mRNA and sequestering eIF4E to block translation-initiation complex assembly [PMID:29358667]. Its activity is gated by phosphorylation, both via the kinase Stk38, which controls RBM24 stability during sarcomere assembly [PMID:28322254], and via eIF4E2–GSK3β-mediated S181 phosphorylation that couples stress signaling to APOE translation and cardiac function [PMID:39580475]. Through these activities RBM24 is required in vivo for cardiac morphogenesis, skeletal muscle regeneration, cochlear hair cell survival and stereocilia integrity, lens and eye development, and adult neurogenesis [PMID:29358667, PMID:33042276, PMID:32887533, PMID:41884985, PMID:31814023, PMID:39113792]. Loss-of-function genetic models additionally implicate RBM24 in tissue-specific splicing relevant to familial dysautonomia and Usher syndrome 1D through regulation of IKBKAP and Cdh23 splicing [PMID:28592461, PMID:32887533].","teleology":[{"year":2009,"claim":"Established that RBM24 is not merely a marker of muscle but a functional driver, coupling cell-cycle arrest to myogenic differentiation.","evidence":"RNAi knockdown and overexpression in C2C12 myoblasts with epistasis to p21","pmids":["19817877"],"confidence":"Medium","gaps":["The molecular RNA targets mediating differentiation were not defined","Mechanism of cell-cycle arrest left at the phenotypic level"]},{"year":2010,"claim":"Placed RBM24 downstream of the master myogenic transcription factor by showing MyoD directly activates its expression through E-box elements.","evidence":"Hormone-inducible MyoD, RBM24 reporter constructs and morpholino knockdown in Xenopus","pmids":["20338237"],"confidence":"Medium","gaps":["Reporter-based E-box activation not confirmed by endogenous occupancy in this study","Downstream RBM24 effectors not identified"]},{"year":2012,"claim":"Demonstrated a required in vivo role in sarcomere assembly and cardiac contractility, anchoring RBM24 in striated muscle development.","evidence":"Zebrafish loss-of-function with expression profiling and sarcomere analysis","pmids":["22345307"],"confidence":"Medium","gaps":["Did not resolve whether the sarcomere defect was splicing-, stability-, or translation-driven","No direct RNA targets identified"]},{"year":2013,"claim":"Defined RBM24 as a sequence-specific mRNA stability regulator acting through AU/U-rich elements, with opposite effects on p21 (stabilized) and p63 (destabilized).","evidence":"RNA-binding assays, RRM/domain mutagenesis and mRNA half-life measurements with overexpression/knockdown","pmids":["24356969","24375645"],"confidence":"High","gaps":["How RBM24 chooses to stabilize versus destabilize a given transcript was not explained","In vivo physiological relevance of p21/p63 regulation not tested"]},{"year":2014,"claim":"Provided the splicing mechanism: RBM24 binding to an intronic splicing enhancer is sufficient to override exonic silencer repression and confer muscle-specific exon inclusion.","evidence":"In vitro splicing in nuclear extracts, recombinant protein, enhancer/silencer mutagenesis, plus mouse knockout, with confirmation of direct MyoD/ChIP control of Rbm24","pmids":["25313962","25217815"],"confidence":"High","gaps":["Genome-wide splicing repertoire not yet mapped","How RBM24 competes with PTB/hnRNP repressors mechanistically not resolved"]},{"year":2016,"claim":"Broadened RBM24's regulatory reach: it drives cardiac-lineage splicing switches (Tpm1), cooperates with RBM20 on intronic targets, is tuned by miR-222, and participates in lncRNA/miRNA feedback circuits.","evidence":"Inducible ESC RNA-seq, co-expression splicing reporters, RISC pulldown and Ago2 Co-IP with rescue experiments","pmids":["26990106","27289039","26844700","27565737"],"confidence":"Medium","gaps":["Combinatorial logic with RBM20 and other RBPs not systematically dissected","Physiological weight of the miRNA feedback loops unquantified"]},{"year":2017,"claim":"Identified phospho-regulation of RBM24 and expanded its mechanistic modes to coding-region binding and tissue-specific cryptic splicing relevant to disease.","evidence":"Co-IP/MS identifying Stk38, kinase activity manipulation, RIP-Chip profiling in cardiomyocytes, and a splicing-reporter screen for IKBKAP","pmids":["28322254","29104163","28592461"],"confidence":"Medium","gaps":["Stk38 phosphosites on RBM24 not mapped in these studies","Causal link between IKBKAP cryptic splicing and familial dysautonomia phenotype shown only in reporter systems"]},{"year":2018,"claim":"Revealed RBM24 as a translational repressor that sequesters eIF4E to block p53 translation, with genetic rescue establishing this as a developmentally essential function.","evidence":"Co-IP of RBM24–eIF4E, translation assays, and Rbm24/p53 double-knockout mouse rescue of endocardial cushion defects","pmids":["29358667","30133047","30076363"],"confidence":"High","gaps":["Structural basis of eIF4E sequestration not determined","Whether cytoplasmic localization is dynamically regulated across tissues left open"]},{"year":2020,"claim":"Established cytoplasmic poly(A)-tail control and nucleocytoplasmic shuttling as core mechanisms, and extended RBM24 function to eye, ear, and muscle regeneration with specific stability/splicing targets.","evidence":"Zebrafish lens Co-IP (Cpeb1b/Pabpc1l) and poly(A) assays, RIP/EMSA for Sox2, conditional KO mice in muscle and inner ear, and fractionation during myogenesis","pmids":["32170011","31814023","33941806","33042276","32887533"],"confidence":"High","gaps":["Signals controlling RBM24's cytoplasm-to-nucleus translocation not identified","How a single protein partitions among splicing, stability, polyadenylation, and translation in a given cell unresolved"]},{"year":2021,"claim":"Confirmed the human splicing mechanism in hESC-derived cardiomyocytes (ACTN2 exon 6) and expanded RBM24's tumor-suppressive and signaling roles via PTEN and Runx1t1 stabilization.","evidence":"CRISPR KO in hESCs with exon-deletion and rescue, plus RIP and KO mouse models for PTEN and bladder cancer feedback loops","pmids":["34816743","34709758","34021255"],"confidence":"High","gaps":["Context-dependence of pro- versus anti-tumor activity across tissues not reconciled","Determinants of RBM24 binding-site specificity (AU-rich vs GT-rich vs coding) still unclear"]},{"year":2022,"claim":"Connected RBM24 splicing to cardiac electrophysiology (CaMKIIδ/QT interval), demonstrated broad-spectrum antiviral translational blockade, and linked it to ferroptosis resistance via SLC7A11.","evidence":"KO mouse and hESC-cardiomyocyte electrophysiology with pharmacological rescue, RNP-submotif binding and 80S assembly assays for SARS-CoV-2/HBV, and SLC7A11 rescue experiments","pmids":["36454480","36464077","29760415","30626666","36478739","27002326"],"confidence":"High","gaps":["Whether the antiviral translational role is physiologically relevant in vivo not established","Structural NMR data not yet linked to specific RNA-recognition mutants"]},{"year":2024,"claim":"Integrated stress signaling, transcriptional control, and neural/cochlear function: GSK3β-mediated S181 phosphorylation gates APOE translation, POU4F3 controls hair-cell Rbm24 expression, and RBM24 sustains brain plasticity and neurogenesis.","evidence":"S181A knock-in mice with APOE rescue, in vivo enhancer reporter and KO analyses (POU4F3, Insm1), and conditional brain/NSPC KO with Notch1 stability and DAPT rescue","pmids":["39580475","38483314","39004256","39113792","41884985"],"confidence":"High","gaps":["Kinase(s) and signals converging on RBM24 phosphosites across tissues incompletely mapped","How phosphorylation switches RBM24 between its many regulatory modes not resolved"]},{"year":2025,"claim":"Extended RBM24 mechanism to circRNA biogenesis and vascular remodeling, showing phosphorylation-dependent circRNA production and JAK2 mRNA stabilization driving VSMC phenotypic switching.","evidence":"circRNA profiling in KO hearts with pre-mRNA binding and phosphorylation manipulation, plus VSMC-specific KO/AAV models with RIP and STAT3 inhibition","pmids":["40250678","41216933"],"confidence":"Medium","gaps":["Direct demonstration that the same phosphosite controls circRNA output and splicing not provided","Relationship between circ23679 and canonical splicing targets unclear"]},{"year":2026,"claim":"Demonstrated that RBM24 itself is alternatively spliced into functionally distinct isoforms whose balance is critical, with both loss of the short isoform and overexpression of the long isoform causing hearing loss.","evidence":"Exon 4 conditional deletion and RBM24-L overexpression mice with hearing tests, hair-cell imaging, and Strc target analysis","pmids":["41973913"],"confidence":"High","gaps":["Differential target preferences of RBM24-S versus RBM24-L not comprehensively mapped","Regulation of RBM24 autoregulatory exon 4 splicing not defined"]},{"year":null,"claim":"How a single RRM protein is partitioned among splicing, mRNA stability, polyadenylation, translation, and circRNA biogenesis in a given cell — and how phosphorylation, isoform identity, and partner availability select among these modes — remains the central open question.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model of binding-site specificity across AU-rich, GT-rich, GUGUG, and coding-region elements","Structural basis of mode-switching not determined","Tissue-specific cofactor landscape incompletely defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,2,3,4,6,16,21,24,28]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,6,20,23]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[4,14,24,32]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,3,21,27]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[6,17,18]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,18]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,6,16,20,23]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[5,7,8,9,30,39]},{"term_id":"R-HSA-397014","term_label":"Muscle contraction","supporting_discovery_ids":[1,20,23]}],"complexes":[],"partners":["EIF4E","STK38","CPEB1","PABPC1L","AGO2","RBM20","GSK3B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BX46","full_name":"RNA-binding protein 24","aliases":["RNA-binding motif protein 24","RNA-binding region-containing protein 6"],"length_aa":236,"mass_kda":24.8,"function":"Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation (PubMed:20977548, PubMed:24375645, PubMed:29104163, PubMed:29358667). Plays a major role in pre-mRNA alternative splicing regulation (PubMed:26990106, PubMed:29104163). Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation (PubMed:29104163). Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing (By similarity). Involved in embryonic stem cell (ESC) transition to cardiac cell differentiation by promoting pre-mRNA alternative splicing events of several pluripotency and/or differentiation genes (PubMed:26990106). Plays a role in the regulation of mRNA stability (PubMed:20977548, PubMed:24356969, PubMed:24375645, PubMed:29104163). Binds to 3'-untranslated region (UTR) AU-rich elements in target transcripts, such as CDKN1A and MYOG, leading to maintain their stabilities (PubMed:20977548, PubMed:24356969). Involved in myogenic differentiation by regulating MYOG levels (PubMed:20977548). Binds to multiple regions in the mRNA 3'-UTR of TP63 isoform 2, hence inducing its destabilization (PubMed:24375645). Also promotes the destabilization of the CHRM2 mRNA via its binding to a region in the coding sequence (PubMed:29104163). Plays a role in the regulation of mRNA translation (PubMed:29358667). Mediates repression of p53/TP53 mRNA translation through its binding to U-rich element in the 3'-UTR, hence preventing EIF4E from binding to p53/TP53 mRNA and translation initiation (PubMed:29358667). Binds to a huge amount of mRNAs (PubMed:29104163). Required for embryonic heart development, sarcomer and M-band formation in striated muscles (By similarity). Together with RBM20, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By similarity) (Microbial infection) Promotes hepatitis C virus (HCV) replication over translation through the inhibition of viral protein expression. Decreases viral translation by linking viral 5'- and 3'-UTRs, blocking 80S ribosome assembly on the viral IRES and enhancing the interaction of the mature core protein and 5'-UTR","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9BX46/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RBM24","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RBM24","total_profiled":1310},"omim":[{"mim_id":"621305","title":"CARDIAC MESODERM ENHANCER-ASSOCIATED NONCODING RNA; CARMN","url":"https://www.omim.org/entry/621305"},{"mim_id":"617603","title":"RNA-BINDING MOTIF PROTEIN 24; RBM24","url":"https://www.omim.org/entry/617603"},{"mim_id":"300569","title":"MICRO RNA 222; MIR222","url":"https://www.omim.org/entry/300569"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"heart muscle","ntpm":132.9},{"tissue":"skeletal muscle","ntpm":293.2},{"tissue":"tongue","ntpm":98.7}],"url":"https://www.proteinatlas.org/search/RBM24"},"hgnc":{"alias_symbol":["FLJ30829","dJ259A10.1"],"prev_symbol":["RNPC6"]},"alphafold":{"accession":"Q9BX46","domains":[{"cath_id":"3.30.70.330","chopping":"11-87","consensus_level":"high","plddt":95.4132,"start":11,"end":87}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BX46","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BX46-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BX46-F1-predicted_aligned_error_v6.png","plddt_mean":66.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RBM24","jax_strain_url":"https://www.jax.org/strain/search?query=RBM24"},"sequence":{"accession":"Q9BX46","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BX46.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BX46/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BX46"}},"corpus_meta":[{"pmid":"25313962","id":"PMC_25313962","title":"RBM24 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macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40250678","citation_count":4,"is_preprint":false},{"pmid":"39004256","id":"PMC_39004256","title":"Rbm24 modulates neuronal RNA splicing to restrict cognitive dysfunction.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39004256","citation_count":4,"is_preprint":false},{"pmid":"35395551","id":"PMC_35395551","title":"RBM24 is localized to stress granules in cells under various stress conditions.","date":"2022","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/35395551","citation_count":4,"is_preprint":false},{"pmid":"39113792","id":"PMC_39113792","title":"Rbm24/Notch1 signaling regulates adult neurogenesis in the subventricular zone and mediates Parkinson-associated olfactory dysfunction.","date":"2024","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/39113792","citation_count":4,"is_preprint":false},{"pmid":"38158676","id":"PMC_38158676","title":"MiR-20a-5p targets RBM24 and alleviates hypertensive intracerebral hemorrhage.","date":"2023","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/38158676","citation_count":4,"is_preprint":false},{"pmid":"36213838","id":"PMC_36213838","title":"RBM24 Mediates Lymph Node Metastasis and Epithelial-Mesenchymal Transition in Human Hypopharyngeal Squamous Cell Carcinoma by Regulating Twist1.","date":"2022","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36213838","citation_count":3,"is_preprint":false},{"pmid":"41216933","id":"PMC_41216933","title":"RBM24 regulates phenotypic switching of smooth muscle cell in vascular remodeling by stabilizing JAK2 mRNA.","date":"2025","source":"Cardiovascular research","url":"https://pubmed.ncbi.nlm.nih.gov/41216933","citation_count":2,"is_preprint":false},{"pmid":"39614020","id":"PMC_39614020","title":"Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, function and regeneration.","date":"2024","source":"Journal of muscle research and cell motility","url":"https://pubmed.ncbi.nlm.nih.gov/39614020","citation_count":2,"is_preprint":false},{"pmid":"38441112","id":"PMC_38441112","title":"YAP1-induced RBM24 promotes the tumorigenesis of triple-negative breast cancer through the β-catenin pathway.","date":"2024","source":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","url":"https://pubmed.ncbi.nlm.nih.gov/38441112","citation_count":2,"is_preprint":false},{"pmid":"38499965","id":"PMC_38499965","title":"RBM24 Suppresses the Tumorigenesis of Glioblastoma by Stabilizing LATS1 mRNA.","date":"2024","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38499965","citation_count":1,"is_preprint":false},{"pmid":"27002326","id":"PMC_27002326","title":"(1)H, (15)N and (13)C backbone and side chain resonance assignments of the RRM domain from human RBM24.","date":"2016","source":"Biomolecular NMR assignments","url":"https://pubmed.ncbi.nlm.nih.gov/27002326","citation_count":1,"is_preprint":false},{"pmid":"35115788","id":"PMC_35115788","title":"lncRNA HAND2-AS1 Regulates Prostate Cancer Cell Growth Through Targeting the miR-106a-5p/RBM24 Axis [Retraction].","date":"2022","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/35115788","citation_count":1,"is_preprint":false},{"pmid":"41973913","id":"PMC_41973913","title":"Alternative splicing of the Rbm24 gene is essential for cochlear hair cell stereocilia integrity and hearing function in mice.","date":"2026","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/41973913","citation_count":0,"is_preprint":false},{"pmid":"40200085","id":"PMC_40200085","title":"RBM24 regulates apoptosis rates by modulating global transcriptome profile in CAL27 cells.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40200085","citation_count":0,"is_preprint":false},{"pmid":"41884985","id":"PMC_41884985","title":"Rbm24 promotes outer hair cell survival through Insm1 repression while independently regulating hair bundle morphogenesis.","date":"2026","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/41884985","citation_count":0,"is_preprint":false},{"pmid":"39957481","id":"PMC_39957481","title":"Genetic screening of the RNA-binding protein RBM24 and its binding sites in the SOX2 3' untranslated region in a cohort of 50 patients with micro-anophthalmia.","date":"2025","source":"Ophthalmic genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39957481","citation_count":0,"is_preprint":false},{"pmid":"41676418","id":"PMC_41676418","title":"Cuproptosis-induced upregulation of RBM24 suppresses tumor metastasis via MAPK signaling blockage in colorectal cancer.","date":"2025","source":"Archives of medical science : AMS","url":"https://pubmed.ncbi.nlm.nih.gov/41676418","citation_count":0,"is_preprint":false},{"pmid":"41729285","id":"PMC_41729285","title":"Promoting mechanisms of papillary thyroid carcinoma by the LncRNA CASC2/miR-193a-3p/RBM24 axis.","date":"2026","source":"Die Naturwissenschaften","url":"https://pubmed.ncbi.nlm.nih.gov/41729285","citation_count":0,"is_preprint":false},{"pmid":"28753211","id":"PMC_28753211","title":"Corrigendum: Stk38 Modulates Rbm24 Protein Stability to Regulate Sarcomere Assembly in Cardiomyocytes.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28753211","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.06.26.600754","title":"Rbm24 maintains survival of cochlear outer hair cells by repressing Insm1","date":"2024-06-29","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.26.600754","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":31909,"output_tokens":9689,"usd":0.120531,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":20110,"output_tokens":5156,"usd":0.114725,"stage2_stop_reason":"end_turn"},"total_usd":0.235256,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"RBM24 is sufficient to promote muscle-specific exon inclusion in nuclear extracts of non-muscle cells; binding of RBM24 to an intronic splicing enhancer (ISE) is essential and sufficient to overcome repression by an exonic splicing silencer (ESS) containing PTB and hnRNP A1/A2 binding sites. Introduction of ESS and ISE converted a constitutive exon into an RBM24-dependent alternative exon.\",\n      \"method\": \"In vitro splicing assays in nuclear extracts; recombinant protein; targeted inactivation in mice; exon reporter constructs\",\n      \"journal\": \"Developmental Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with recombinant protein, mutagenesis of enhancer/silencer elements, and in vivo mouse knockout with defined phenotypic readout\",\n      \"pmids\": [\"25313962\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Rbm24 loss-of-function in zebrafish causes reduction in sarcomeric proteins, Z-disc abnormality, and diminished heart contractility, establishing a required role for Rbm24 in sarcomere assembly and cardiac function.\",\n      \"method\": \"Zebrafish loss-of-function; gene expression profiling; protein analysis\",\n      \"journal\": \"Cardiovascular Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown in vertebrate model with defined sarcomere and contractility phenotype, single lab\",\n      \"pmids\": [\"22345307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"RBM24 binds to the 3'-UTR of p21 transcript via an AU/U-rich element and stabilizes p21 mRNA, increasing p21 half-life and protein levels. The RNA recognition motif (RRM) of RBM24 is required for this binding and p21 upregulation.\",\n      \"method\": \"mRNA stability assay; RBM24 overexpression/knockdown; RRM domain mutagenesis; RNA binding assay\",\n      \"journal\": \"Journal of Biological Chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro binding with domain mutagenesis, mRNA half-life measurements, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24356969\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"RBM24 binds to multiple regions in the p63 3'-UTR and destabilizes p63 transcript, decreasing p63 mRNA and protein levels. The 3'-UTR of p63 and the RNA-binding domain of RBM24 are both required for this regulatory interaction.\",\n      \"method\": \"RBM24 overexpression/knockdown; RNA binding assay; mRNA stability assay; domain deletion analysis\",\n      \"journal\": \"Molecular Cancer Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA binding demonstrated, domain requirements defined, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24375645\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Rbm24, a p53 target gene, regulates p53 mRNA translation by binding to p53 mRNA and interacting with translation initiation factor eIF4E, preventing eIF4E from binding to p53 mRNA and inhibiting assembly of the translation initiation complex. Rbm24-null mice die in utero with endocardial cushion defects partially rescued by p53 deficiency.\",\n      \"method\": \"Co-immunoprecipitation (RBM24–eIF4E interaction); RNA-binding assay; translation assay; Rbm24/p53 double-knockout mouse rescue\",\n      \"journal\": \"Cell Death and Differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP interaction, translation assay, genetic rescue by p53 KO; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"29358667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Rbm24 overexpression induces cell cycle arrest and promotes myogenic differentiation in C2C12 cells; knockdown delays differentiation and suppresses cell cycle arrest. Unlike Rbm38 (which binds p21 transcript), the p21-independent pathway of Rbm24 mediates this effect.\",\n      \"method\": \"RNA interference knockdown; overexpression in C2C12 cells; immunoprecipitation-RT-PCR\",\n      \"journal\": \"Genes to Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional KD/OE with defined phenotype, single lab; mechanistic pathway partially defined via epistasis with p21\",\n      \"pmids\": [\"19817877\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In zebrafish lens, Rbm24 binds broadly to lens-specific mRNAs via its RRM domain, interacts with cytoplasmic polyadenylation element-binding protein (Cpeb1b) and cytoplasmic poly(A)-binding protein (Pabpc1l) via its C-terminal region, and controls poly(A) tail length of crystallin mRNAs. Loss of Rbm24 shortens poly(A) tails of crystallin mRNAs and reduces their translation, impairing lens transparency.\",\n      \"method\": \"Zebrafish rbm24 loss-of-function; co-immunoprecipitation; poly(A) tail length assay; RRM domain functional analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP showing Rbm24-Cpeb1b-Pabpc1l complex, poly(A) length assay, domain analysis, and developmental phenotype; multiple orthogonal methods\",\n      \"pmids\": [\"32170011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Xenopus Seb4/RBM24 expression is directly regulated by MyoD; a 0.65 kb RBM24 regulatory region containing E-boxes is activated by MyoD in reporter assays. Knockdown of Seb4 inhibits myogenic gene expression and myogenesis induced by MyoD.\",\n      \"method\": \"Hormone-inducible MyoD; RBM24 reporter construct injection; morpholino knockdown in Xenopus\",\n      \"journal\": \"Mechanisms of Development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay with MyoD E-box, morpholino KD with defined myogenic phenotype, single lab\",\n      \"pmids\": [\"20338237\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Rbm24 protein expression is directly regulated by MyoD in vivo (ChIP assay in chick embryo); Rbm24 accumulates in MyoD-positive myoblasts and is required for somitic myogenic progenitor cells to differentiate into muscle cells.\",\n      \"method\": \"In vivo chromatin immunoprecipitation (ChIP); morpholino knockdown; immunofluorescence\",\n      \"journal\": \"Mechanisms of Development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct ChIP evidence for MyoD binding, morpholino KD with differentiation phenotype, single lab\",\n      \"pmids\": [\"25217815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Rbm24 regulates alternative splicing switch in ESC cardiac lineage differentiation; forced Rbm24 expression in ESCs dramatically induces cardiac specification and switches splicing of pluripotency genes including Tpm1, whose ESC/tissue-specific isoforms are functionally distinct and required for differentiation.\",\n      \"method\": \"Inducible mouse ESC line; genome-wide RNA-seq; forced expression; functional isoform comparison\",\n      \"journal\": \"Stem Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide splicing analysis, functional validation of Tpm1 isoforms, single lab\",\n      \"pmids\": [\"26990106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MicroRNA-222 targets Rbm24 mRNA; downregulation of Rbm24 by miR-222 results in defective exon inclusion in Coro6, Fxr1, and NACA muscle-specific transcripts. Reconstitution of Rbm24 in miR-222-overexpressing cells rescues muscle-specific splicing.\",\n      \"method\": \"RISC pulldown + RNA-seq; miR-222 overexpression; Rbm24 rescue experiment; splicing assays\",\n      \"journal\": \"Cell Death & Disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RISC pulldown identifies Rbm24 as miR-222 target, splicing rescue confirms pathway, single lab\",\n      \"pmids\": [\"26844700\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"RBM20 and RBM24 cooperatively promote expression of short ENH splice variants by binding the 5' intronic region of exon 11 of the enh gene, which contains an in-phase stop codon.\",\n      \"method\": \"Co-expression of RBM20 and RBM24; splicing reporter; RNA binding assay\",\n      \"journal\": \"FEBS Letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding to intronic region demonstrated, cooperative splicing effect shown, single lab\",\n      \"pmids\": [\"27289039\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Stk38 (serine/threonine kinase 38) is an endogenous binding partner of Rbm24 (identified by Co-IP/MS); Stk38 kinase activity-dependently regulates Rbm24 protein stability and phosphorylation in cardiomyocytes. Stk38 knockdown reduces Rbm24 protein levels and impairs sarcomere assembly.\",\n      \"method\": \"Co-immunoprecipitation coupled with mass spectrometry; kinase inhibitor/activator; Stk38 knockdown; sarcomere analysis\",\n      \"journal\": \"Scientific Reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP/MS identifies interaction, kinase activity-dependent regulation confirmed with inhibitor/activator, single lab\",\n      \"pmids\": [\"28322254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RBM24 functions as a cryptic intronic splicing enhancer by binding to an element (IVS20+13-29) downstream of the FD-associated 5' splice site mutation in IKBKAP and promotes U1 snRNP recognition specifically at the mutated (not wild-type) 5' splice site, explaining neuron-specific aberrant splicing in familial dysautonomia.\",\n      \"method\": \"Mammalian dual-color splicing reporter screen; RBP expression library screen; direct binding assay\",\n      \"journal\": \"RNA\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional splicing reporter with defined binding element, specificity for mutant vs WT site demonstrated, single lab\",\n      \"pmids\": [\"28592461\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"RBM24 interacts with both the 5' and 3' terminal redundancy (TR) sequences of HBV 3.5-kb RNA via its RNA-binding domains. Interaction with 5' TR blocks 80S ribosome assembly on HBV pgRNA, inhibiting core protein translation; interaction with 3' TR enhances HBV RNA stability.\",\n      \"method\": \"RNA-binding domain interaction assays; 80S ribosome assembly assay; HBV transfection/infection cell model; RBM24 overexpression/knockdown\",\n      \"journal\": \"Emerging Microbes & Infections\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistically distinct dual functions demonstrated with ribosome assembly assay and RNA stability measurement, single lab\",\n      \"pmids\": [\"29760415\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"RBM24 directly binds the lower bulge of the epsilon stem-loop of HBV pgRNA via RNP submotifs, and interacts with HBV polymerase (Pol) in an RNA-independent manner via its alanine-rich domain (ARD) and the Pol reverse transcriptase (RT) domain. RBM24 forms a Pol-RBM24-ε complex that mediates Pol-ε interaction and promotes pgRNA packaging.\",\n      \"method\": \"Co-immunoprecipitation; RNA binding assays; domain deletion mutants; pgRNA packaging efficiency assay\",\n      \"journal\": \"Journal of Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mapping of protein-protein and protein-RNA interactions, functional packaging assay, single lab\",\n      \"pmids\": [\"30626666\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RBM24 protein binds Sox2 mRNA in mouse embryonic eye tissue (RNA immunoprecipitation) and directly binds the Sox2 mRNA 3'-UTR via AU-rich elements (EMSA). RBM24 elevates Sox2 mRNA half-life in an ARE-dependent manner. Loss of Rbm24 downregulates SOX2 and causes microphthalmia/anophthalmia.\",\n      \"method\": \"RNA immunoprecipitation (RIP) from mouse embryonic tissue; electrophoretic mobility shift assay (EMSA); mRNA half-life assay; CRISPR and morpholino knockdown in mouse and zebrafish\",\n      \"journal\": \"Human Molecular Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RIP in vivo plus EMSA with ARE mutagenesis plus mRNA stability assay plus genetic models in two species; multiple orthogonal methods\",\n      \"pmids\": [\"31814023\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Rbm24 displays cytoplasmic localization in lens, olfactory epithelium, and mechanosensory cells of auditory and vestibular systems during mouse development, consistent with cytoplasmic post-transcriptional regulatory activity in these tissues.\",\n      \"method\": \"Immunostaining and subcellular localization analysis in mouse embryo sections\",\n      \"journal\": \"Developmental Dynamics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization data only, no functional consequence directly demonstrated in this study\",\n      \"pmids\": [\"30133047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"During C2C12 myoblast differentiation, Rbm24 undergoes cytoplasm-to-nucleus translocation. In regenerating adult muscle, Rbm24 accumulates in the myonucleus of nascent myofibers. Early in regeneration Rbm24 is required for myogenin expression; late in regeneration it regulates muscle-specific pre-mRNA alternative splicing.\",\n      \"method\": \"Subcellular fractionation/immunofluorescence during differentiation; satellite cell transplantation; injury-induced regeneration model\",\n      \"journal\": \"Scientific Reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular localization with functional consequence (myogenin expression vs. splicing at distinct stages); satellite cell transplantation provides causal evidence; single lab\",\n      \"pmids\": [\"33941806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Rbm24 conditional knockout in skeletal muscle and satellite cells impairs myogenic fusion and differentiation, delays muscle regeneration after cardiotoxin injury, and dysregulates alternative splicing of Mef2d, Naca, Rock2, and Lrrfip1.\",\n      \"method\": \"Conditional knockout mice (skeletal muscle-specific and satellite cell-specific); CTX injury model; RNA-seq\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-type-specific KO with defined regeneration phenotype and target splicing events identified, single lab\",\n      \"pmids\": [\"33042276\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM24 ablation in hESCs (CRISPR/Cas9) disrupts sarcomere assembly: core myofibrillogenesis proteins (ACTN2, TTN, MYH10) are misspliced, MYH6 cannot replace MYH10, and myofibrillogenesis arrests at the premyofibril stage. RBM24 promotes inclusion of ACTN2 exon 6 (actin-binding domain), and CRISPR deletion of exon 6 or forced expression of full-length ACTN2 in RBM24-/- hESCs confirms exon 6 inclusion is critical for sarcomere assembly.\",\n      \"method\": \"CRISPR/Cas9 KO in hESCs; transcriptomics; ACTN2 exon 6 CRISPR deletion; forced full-length ACTN2 rescue\",\n      \"journal\": \"Circulation Research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO in human cells, specific splicing target identified, exon deletion and rescue experiments converge on mechanism; multiple orthogonal methods\",\n      \"pmids\": [\"34816743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM24 directly binds the GT-rich region (positions 8101-8251) in the 3'-UTR of PTEN mRNA (RIP assay), prolongs PTEN mRNA half-life, and increases PTEN protein levels, suppressing PI3K-Akt signaling. Rbm24-knockout mice develop spontaneous colorectal adenomas with lower PTEN expression.\",\n      \"method\": \"RNA immunoprecipitation; mRNA stability assay; Rbm24 KO mouse model; APC-min mouse model\",\n      \"journal\": \"Clinical and Translational Medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP defines binding site, half-life assay confirms stabilization, in vivo KO phenotype; single lab\",\n      \"pmids\": [\"34709758\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RBM24 positively regulates Runx1t1 mRNA stability in bladder cancer cells by directly binding Runx1t1 mRNA; miR-625-5p directly targets and suppresses RBM24 expression; Runx1t1 promotes RBM24 expression via TCF4-mediated suppression of miR-625-5p, forming a positive feedback loop.\",\n      \"method\": \"RNA immunoprecipitation; luciferase reporter; mRNA stability assay; gain/loss-of-function\",\n      \"journal\": \"Experimental & Molecular Medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP and luciferase confirm direct binding, feedback loop validated by multiple assays, single lab\",\n      \"pmids\": [\"34021255\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RBM24 ablation in mice and hESC-derived cardiomyocytes causes aberrant shift of CaMKIIδ splicing towards the δ-C isoform, leading to altered Ca2+ handling, prolongation of ventricular action potential and QT interval. CaMKIIδ inhibitor treatment attenuates these electrophysiological abnormalities.\",\n      \"method\": \"RBM24 knockout mice; hESC-derived cardiomyocyte KD; electrophysiology; CaMKIIδ inhibitor rescue\",\n      \"journal\": \"Cellular and Molecular Life Sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO mouse and human cell model converge on same splicing event and electrophysiological phenotype; pharmacological rescue confirms mechanism; multiple orthogonal methods\",\n      \"pmids\": [\"36454480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RBM24 recognizes and binds to the GUGUG element at stem-loop 4 (SL4) in the 5'-UTR of SARS-CoV-2 RNA via its RNP submotifs, prevents 80S ribosome assembly, and inhibits viral polyprotein translation and replication.\",\n      \"method\": \"RNA binding assay (RNP submotif mapping); 80S ribosome assembly assay; viral replication assay\",\n      \"journal\": \"Antiviral Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — specific binding element mapped, ribosome assembly inhibition demonstrated, single lab\",\n      \"pmids\": [\"36464077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RBM24 regulates mRNA stability of SLC7A11 (a ferroptosis inhibitor); overexpression of RBM24 protects cells from Erastin-induced ferroptosis while knockout sensitizes cells. RBM24 deficiency in mice leads to chronic inflammation and liver steatosis.\",\n      \"method\": \"RBM24 overexpression/knockout; Erastin-induced ferroptosis assay; SLC7A11 knockdown rescue; lipidomics; mouse model\",\n      \"journal\": \"Frontiers in Cell and Developmental Biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue (SLC7A11 KD reverses RBM24 effect), in vivo mouse phenotype, single lab\",\n      \"pmids\": [\"36478739\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"RBM24 protein binds to MIR143HG RNA, destabilizes its transcript and facilitates its interaction with Ago2 to accelerate MIR143HG degradation. RBM24 also promotes biogenesis of miR-143 (evidenced by siRNA against DROSHA). MIR143HG in turn sponges miR-143 (which targets RBM24 mRNA), forming a negative feedback loop.\",\n      \"method\": \"RNA binding assay; mRNA stability assay; Ago2 co-immunoprecipitation; DROSHA siRNA; luciferase reporter\",\n      \"journal\": \"Biochimica et Biophysica Acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein-RNA binding and Ago2 interaction demonstrated, negative feedback loop validated by multiple assays, single lab\",\n      \"pmids\": [\"27565737\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Global RNA immunoprecipitation–microarray (RIP-Chip) profiling of Rbm24 in cardiomyocytes identifies its mRNA binding repertoire. Beyond splicing and mRNA stabilization, Rbm24 destabilizes Chrm2 mRNA via binding a coding-region element, and drives generation of isoforms with alternative transcriptional start sites.\",\n      \"method\": \"RNA immunoprecipitation coupled to microarray (RIP-Chip); mRNA stability assay; coding-region binding validation\",\n      \"journal\": \"The International Journal of Biochemistry & Cell Biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide RIP-Chip with follow-up validation of novel Chrm2 coding-region binding and alternative TSS regulation; single lab\",\n      \"pmids\": [\"29104163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NMR backbone and side-chain resonance assignments of the RRM domain of human RBM24 confirm the canonical RRM domain architecture by secondary chemical shift analysis and relaxation measurements.\",\n      \"method\": \"NMR spectroscopy (1H, 15N, 13C chemical shift assignments; secondary chemical shift analysis; relaxation measurements)\",\n      \"journal\": \"Biomolecular NMR Assignments\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — structural characterization of RRM domain by NMR, single paper, no functional mutagenesis in this study\",\n      \"pmids\": [\"27002326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"AAV9-mediated overexpression of Rbm24 in adult mouse heart induces cardiac fibrosis associated with increased TGFβ-signaling genes (TgfβR1, TgfβR2), periostin expression, and fibroblast activation; it also causes splicing changes in PDZ and Lim domain 5, Phospholamban, and Titin, but not in embryonic Rbm24 splicing targets (skNAC, αNAC, Coro6).\",\n      \"method\": \"AAV9 delivery in adult mice; high-resolution microarrays; histology; gene expression analysis\",\n      \"journal\": \"Scientific Reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo gain-of-function with genome-wide splicing and expression profiling, single lab\",\n      \"pmids\": [\"30076363\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Rbm24 knockout in mice results in hearing loss and balance deficits; Rbm24 regulates inner-ear-specific alternative splicing including direct regulation of Cdh23 splicing (responsible for Usher syndrome 1D), and loss causes stereocilia integrity defects and hair cell death.\",\n      \"method\": \"Rbm24 conditional KO mice; auditory testing; RNA-seq splicing analysis; hair cell imaging\",\n      \"journal\": \"RNA Biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined auditory phenotype, specific splicing target (Cdh23) validated, single lab\",\n      \"pmids\": [\"32887533\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RBM24 is recruited into stress granules under various stress conditions; RBM24 overexpression alone is sufficient to induce stress granule formation. However, knockdown of Rbm24 does not affect stress granule formation.\",\n      \"method\": \"Immunofluorescence under stress; RBM24 overexpression; Rbm24 knockdown\",\n      \"journal\": \"Biochemical and Biophysical Research Communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization to SGs shown, induction by OE demonstrated, but functional consequence of SG localization not mechanistically established; single lab\",\n      \"pmids\": [\"35395551\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling; S181 phosphorylation of RBM24 promotes APOE translation. Rbm24 S181A knock-in mice show cardiac contractile dysfunction, atrial fibrillation, dyslipidemia, and sudden death under stress; cardiomyocyte-specific APOE expression rescues cardiac electrophysiological and contractile defects via preventing ROS stress and mitochondrial dysfunction.\",\n      \"method\": \"Rbm24 S181A knock-in mice; eIF4E2-GSK3β signaling pathway analysis; APOE translation assay; cardiomyocyte-specific APOE rescue; electrophysiology; mitochondria/ROS assays\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — phospho-specific KI mouse model, pathway dissection (eIF4E2-GSK3β), translational target identified (APOE), genetic rescue with APOE; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"39580475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"POU4F3 directly binds three Rbm24 enhancers in cochlear hair cells (identified by transgenic reporter assays), and Rbm24 expression is completely absent in Pou4f3-null hair cells. GFI1 does not regulate Rbm24 expression. Ectopic Rbm24 alone cannot prevent Pou4f3-null hair cells from degenerating.\",\n      \"method\": \"In vivo transgenic reporter assay; Pou4f3 and Gfi1 KO mouse analysis; ectopic Rbm24 expression in Pou4f3-KO\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct enhancer binding by POU4F3 identified by in vivo reporter assay with genetic rescue testing, single lab\",\n      \"pmids\": [\"38483314\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RBM24 knockout in mouse brain impairs learning and memory; Rbm24 regulates alternative splicing of synapse-associated genes GluR2 and Prrt1. Rbm24 deletion disrupts excitatory synaptic function and plasticity in hippocampal slices.\",\n      \"method\": \"Conditional RBM24 KO mice; electrophysiology (hippocampal slices); RNA-seq splicing analysis; behavioral assays\",\n      \"journal\": \"International Journal of Biological Macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined synaptic and behavioral phenotype, specific splicing targets (GluR2, Prrt1) identified; single lab\",\n      \"pmids\": [\"39004256\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Rbm24 maintains Notch1 mRNA stability in adult neural stem/progenitor cells (NSPCs) in the SVZ; Rbm24 deletion impairs NSPC proliferation and neurogenesis in the olfactory bulb. Overexpression of Rbm24 rescues adult neurogenesis and olfactory dysfunction in PD mice, and this rescue is blocked by the Notch1 inhibitor DAPT.\",\n      \"method\": \"Rbm24 KO mice; Rbm24 overexpression in PD mouse model; DAPT pharmacological inhibition; RNA-seq; immunofluorescence; electrophysiology\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mRNA stability target identified, genetic and pharmacological rescue converge, single lab\",\n      \"pmids\": [\"39113792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM24 stabilizes JAK2 mRNA (via RNA immunoprecipitation and luciferase reporter assays) and promotes JAK2-STAT3-KLF4 signaling to drive VSMC phenotypic switching and vascular remodeling. VSMC-specific Rbm24 KO attenuates neointima formation; AAV-mediated RBM24 overexpression promotes it.\",\n      \"method\": \"VSMC-specific KO mice; AAV overexpression; mRNA stability assay; RNA immunoprecipitation; luciferase reporter; STAT3 inhibition (shRNA and nifuroxazide)\",\n      \"journal\": \"Cardiovascular Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RIP confirms JAK2 mRNA binding, stability assay confirms mechanism, genetic and pharmacological rescue; single lab\",\n      \"pmids\": [\"41216933\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RBM24 directly binds pre-mRNA and facilitates exon inclusion to provide substrate for circ23679 production; RBM24-regulated circRNA production depends on its phosphorylation status. Circ23679 acts as a sponge for miR-15b-5p to inhibit cardiac apoptosis.\",\n      \"method\": \"circRNA profiling in Rbm24 KO mouse hearts; RBM24 pre-mRNA binding assay; phosphorylation manipulation; circ23679 overexpression in heart failure model\",\n      \"journal\": \"International Journal of Biological Macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct pre-mRNA binding shown, phosphorylation-dependence of circRNA production demonstrated, functional rescue in heart failure model; single lab\",\n      \"pmids\": [\"40250678\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Rbm24 exon 4 is alternatively spliced to produce a short isoform (RBM24-S) that, while sharing the same RRM, binds different mRNA targets affecting their splicing and/or stability compared to RBM24-L. Deletion of exon 4 (abolishing RBM24-S) causes severe hearing loss in both homozygous and heterozygous mice and stereocilia disorganization. Overexpression of RBM24-L in hair cells also causes stereocilia defects and profound hearing loss, demonstrating that proper balance of isoforms is critical.\",\n      \"method\": \"Exon 4 conditional deletion in mice; RBM24-L overexpression; hearing tests; hair cell imaging; RNA-seq target analysis (Strc)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — isoform-specific exon deletion model plus gain-of-function overexpression model converge on stereocilia and hearing phenotype; target mRNA (Strc) identified; multiple orthogonal models\",\n      \"pmids\": [\"41973913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Rbm24 represses Insm1 expression in cochlear outer hair cells; in Rbm24-null OHCs, Insm1 remains aberrantly expressed and drives OHC death. Simultaneous inactivation of Rbm24 and Insm1 largely rescues OHC survival but only partially restores hair bundle morphology, demonstrating that Rbm24 promotes OHC survival via Insm1 repression independently of its role in hair bundle morphogenesis.\",\n      \"method\": \"Rbm24-/- mouse; Insm1 overexpression; Rbm24/Insm1 double KO; transcriptomic profiling of purified OHCs\",\n      \"journal\": \"Development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — double KO genetic rescue separates two functions (survival vs. morphogenesis), corroborated by transcriptomics and Insm1 overexpression phenocopy; multiple orthogonal approaches\",\n      \"pmids\": [\"41884985\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RBM24 is a highly conserved, tissue-restricted RNA-binding protein that acts through its RRM domain to regulate multiple post-transcriptional mechanisms — including pre-mRNA alternative splicing (promoting muscle-, cardiac-, and inner-ear-specific exon inclusion), mRNA stability (stabilizing p21, Sox2, PTEN, Notch1, JAK2; destabilizing p63, Chrm2), cytoplasmic polyadenylation (controlling poly(A) tail length of crystallin mRNAs via interaction with Cpeb1b and Pabpc1l), and translation (inhibiting p53 and viral polyprotein translation by blocking eIF4E or 80S ribosome assembly); its activity and stability are regulated by phosphorylation (Stk38 kinase; GSK3β-mediated S181 phosphorylation linking stress signaling to APOE translation), and it is transcriptionally controlled by MyoD via E-box elements, making it a master post-transcriptional regulator of cardiac and skeletal muscle development, inner ear function, lens differentiation, and neural homeostasis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RBM24 is a tissue-restricted RNA-binding protein that functions as a master post-transcriptional regulator of striated muscle, inner ear, lens, and neural development through its RRM domain [#0, #20, #28]. In the nucleus it directs tissue-specific alternative splicing: it binds intronic splicing enhancers to overcome silencer-mediated repression and promote muscle-specific exon inclusion [#0], and is required for correct splicing of sarcomeric and cardiac transcripts including ACTN2 exon 6 and CaMKIIδ, with loss arresting myofibrillogenesis at the premyofibril stage and prolonging the ventricular action potential [#20, #23]. RBM24 expression is itself activated by the myogenic transcription factor MyoD via E-box elements, integrating it into the muscle differentiation program where it promotes cell-cycle exit and differentiation [#7, #8, #5]. In the cytoplasm RBM24 controls mRNA fate by sequence-specific binding to AU/U-rich and GT-rich elements: it stabilizes p21, Sox2, PTEN, Notch1 and JAK2 transcripts and destabilizes p63 and Chrm2 [#2, #16, #21, #35, #36, #3, #27], and it controls poly(A) tail length of crystallin mRNAs through a complex with Cpeb1b and Pabpc1l to drive lens transparency [#6]. It additionally regulates translation, binding p53 mRNA and sequestering eIF4E to block translation-initiation complex assembly [#4]. Its activity is gated by phosphorylation, both via the kinase Stk38, which controls RBM24 stability during sarcomere assembly [#12], and via eIF4E2–GSK3β-mediated S181 phosphorylation that couples stress signaling to APOE translation and cardiac function [#32]. Through these activities RBM24 is required in vivo for cardiac morphogenesis, skeletal muscle regeneration, cochlear hair cell survival and stereocilia integrity, lens and eye development, and adult neurogenesis [#4, #19, #30, #39, #16, #35]. Loss-of-function genetic models additionally implicate RBM24 in tissue-specific splicing relevant to familial dysautonomia and Usher syndrome 1D through regulation of IKBKAP and Cdh23 splicing [#13, #30].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established that RBM24 is not merely a marker of muscle but a functional driver, coupling cell-cycle arrest to myogenic differentiation.\",\n      \"evidence\": \"RNAi knockdown and overexpression in C2C12 myoblasts with epistasis to p21\",\n      \"pmids\": [\"19817877\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The molecular RNA targets mediating differentiation were not defined\", \"Mechanism of cell-cycle arrest left at the phenotypic level\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Placed RBM24 downstream of the master myogenic transcription factor by showing MyoD directly activates its expression through E-box elements.\",\n      \"evidence\": \"Hormone-inducible MyoD, RBM24 reporter constructs and morpholino knockdown in Xenopus\",\n      \"pmids\": [\"20338237\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reporter-based E-box activation not confirmed by endogenous occupancy in this study\", \"Downstream RBM24 effectors not identified\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstrated a required in vivo role in sarcomere assembly and cardiac contractility, anchoring RBM24 in striated muscle development.\",\n      \"evidence\": \"Zebrafish loss-of-function with expression profiling and sarcomere analysis\",\n      \"pmids\": [\"22345307\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not resolve whether the sarcomere defect was splicing-, stability-, or translation-driven\", \"No direct RNA targets identified\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined RBM24 as a sequence-specific mRNA stability regulator acting through AU/U-rich elements, with opposite effects on p21 (stabilized) and p63 (destabilized).\",\n      \"evidence\": \"RNA-binding assays, RRM/domain mutagenesis and mRNA half-life measurements with overexpression/knockdown\",\n      \"pmids\": [\"24356969\", \"24375645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How RBM24 chooses to stabilize versus destabilize a given transcript was not explained\", \"In vivo physiological relevance of p21/p63 regulation not tested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Provided the splicing mechanism: RBM24 binding to an intronic splicing enhancer is sufficient to override exonic silencer repression and confer muscle-specific exon inclusion.\",\n      \"evidence\": \"In vitro splicing in nuclear extracts, recombinant protein, enhancer/silencer mutagenesis, plus mouse knockout, with confirmation of direct MyoD/ChIP control of Rbm24\",\n      \"pmids\": [\"25313962\", \"25217815\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide splicing repertoire not yet mapped\", \"How RBM24 competes with PTB/hnRNP repressors mechanistically not resolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Broadened RBM24's regulatory reach: it drives cardiac-lineage splicing switches (Tpm1), cooperates with RBM20 on intronic targets, is tuned by miR-222, and participates in lncRNA/miRNA feedback circuits.\",\n      \"evidence\": \"Inducible ESC RNA-seq, co-expression splicing reporters, RISC pulldown and Ago2 Co-IP with rescue experiments\",\n      \"pmids\": [\"26990106\", \"27289039\", \"26844700\", \"27565737\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Combinatorial logic with RBM20 and other RBPs not systematically dissected\", \"Physiological weight of the miRNA feedback loops unquantified\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified phospho-regulation of RBM24 and expanded its mechanistic modes to coding-region binding and tissue-specific cryptic splicing relevant to disease.\",\n      \"evidence\": \"Co-IP/MS identifying Stk38, kinase activity manipulation, RIP-Chip profiling in cardiomyocytes, and a splicing-reporter screen for IKBKAP\",\n      \"pmids\": [\"28322254\", \"29104163\", \"28592461\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stk38 phosphosites on RBM24 not mapped in these studies\", \"Causal link between IKBKAP cryptic splicing and familial dysautonomia phenotype shown only in reporter systems\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed RBM24 as a translational repressor that sequesters eIF4E to block p53 translation, with genetic rescue establishing this as a developmentally essential function.\",\n      \"evidence\": \"Co-IP of RBM24–eIF4E, translation assays, and Rbm24/p53 double-knockout mouse rescue of endocardial cushion defects\",\n      \"pmids\": [\"29358667\", \"30133047\", \"30076363\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of eIF4E sequestration not determined\", \"Whether cytoplasmic localization is dynamically regulated across tissues left open\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established cytoplasmic poly(A)-tail control and nucleocytoplasmic shuttling as core mechanisms, and extended RBM24 function to eye, ear, and muscle regeneration with specific stability/splicing targets.\",\n      \"evidence\": \"Zebrafish lens Co-IP (Cpeb1b/Pabpc1l) and poly(A) assays, RIP/EMSA for Sox2, conditional KO mice in muscle and inner ear, and fractionation during myogenesis\",\n      \"pmids\": [\"32170011\", \"31814023\", \"33941806\", \"33042276\", \"32887533\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signals controlling RBM24's cytoplasm-to-nucleus translocation not identified\", \"How a single protein partitions among splicing, stability, polyadenylation, and translation in a given cell unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Confirmed the human splicing mechanism in hESC-derived cardiomyocytes (ACTN2 exon 6) and expanded RBM24's tumor-suppressive and signaling roles via PTEN and Runx1t1 stabilization.\",\n      \"evidence\": \"CRISPR KO in hESCs with exon-deletion and rescue, plus RIP and KO mouse models for PTEN and bladder cancer feedback loops\",\n      \"pmids\": [\"34816743\", \"34709758\", \"34021255\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Context-dependence of pro- versus anti-tumor activity across tissues not reconciled\", \"Determinants of RBM24 binding-site specificity (AU-rich vs GT-rich vs coding) still unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected RBM24 splicing to cardiac electrophysiology (CaMKIIδ/QT interval), demonstrated broad-spectrum antiviral translational blockade, and linked it to ferroptosis resistance via SLC7A11.\",\n      \"evidence\": \"KO mouse and hESC-cardiomyocyte electrophysiology with pharmacological rescue, RNP-submotif binding and 80S assembly assays for SARS-CoV-2/HBV, and SLC7A11 rescue experiments\",\n      \"pmids\": [\"36454480\", \"36464077\", \"29760415\", \"30626666\", \"36478739\", \"27002326\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the antiviral translational role is physiologically relevant in vivo not established\", \"Structural NMR data not yet linked to specific RNA-recognition mutants\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Integrated stress signaling, transcriptional control, and neural/cochlear function: GSK3β-mediated S181 phosphorylation gates APOE translation, POU4F3 controls hair-cell Rbm24 expression, and RBM24 sustains brain plasticity and neurogenesis.\",\n      \"evidence\": \"S181A knock-in mice with APOE rescue, in vivo enhancer reporter and KO analyses (POU4F3, Insm1), and conditional brain/NSPC KO with Notch1 stability and DAPT rescue\",\n      \"pmids\": [\"39580475\", \"38483314\", \"39004256\", \"39113792\", \"41884985\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase(s) and signals converging on RBM24 phosphosites across tissues incompletely mapped\", \"How phosphorylation switches RBM24 between its many regulatory modes not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended RBM24 mechanism to circRNA biogenesis and vascular remodeling, showing phosphorylation-dependent circRNA production and JAK2 mRNA stabilization driving VSMC phenotypic switching.\",\n      \"evidence\": \"circRNA profiling in KO hearts with pre-mRNA binding and phosphorylation manipulation, plus VSMC-specific KO/AAV models with RIP and STAT3 inhibition\",\n      \"pmids\": [\"40250678\", \"41216933\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct demonstration that the same phosphosite controls circRNA output and splicing not provided\", \"Relationship between circ23679 and canonical splicing targets unclear\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated that RBM24 itself is alternatively spliced into functionally distinct isoforms whose balance is critical, with both loss of the short isoform and overexpression of the long isoform causing hearing loss.\",\n      \"evidence\": \"Exon 4 conditional deletion and RBM24-L overexpression mice with hearing tests, hair-cell imaging, and Strc target analysis\",\n      \"pmids\": [\"41973913\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Differential target preferences of RBM24-S versus RBM24-L not comprehensively mapped\", \"Regulation of RBM24 autoregulatory exon 4 splicing not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single RRM protein is partitioned among splicing, mRNA stability, polyadenylation, translation, and circRNA biogenesis in a given cell — and how phosphorylation, isoform identity, and partner availability select among these modes — remains the central open question.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model of binding-site specificity across AU-rich, GT-rich, GUGUG, and coding-region elements\", \"Structural basis of mode-switching not determined\", \"Tissue-specific cofactor landscape incompletely defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 2, 3, 4, 6, 16, 21, 24, 28]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 6, 20, 23]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [4, 14, 24, 32]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 3, 21, 27]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [6, 17, 18]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 18]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 6, 16, 20, 23]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5, 7, 8, 9, 30, 39]},\n      {\"term_id\": \"R-HSA-397014\", \"supporting_discovery_ids\": [1, 20, 23]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EIF4E\", \"STK38\", \"CPEB1\", \"PABPC1L\", \"AGO2\", \"RBM20\", \"GSK3B\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}