Affinage

RBM23

Probable RNA-binding protein 23 · UniProt Q86U06

Length
439 aa
Mass
48.7 kDa
Annotated
2026-06-10
14 papers in source corpus 6 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM23 (CAPERbeta) is a nuclear RNA-binding protein that functions both as a transcriptional coactivator of steroid hormone receptors, including the progesterone receptor, and as a regulator of alternative pre-mRNA splicing, with these two activities residing in distinct, separable domains (PMID:15694343). Its RRM2 domain harbors a degron motif shared exclusively with RBM39 among human proteins; in the presence of aryl sulfonamide molecular glues (indisulam, E7820, tasisulam), this motif mediates recruitment to the CRL4-DCAF15 E3 ubiquitin ligase complex, driving RBM23 ubiquitination and proteasomal degradation, as resolved by crystal and cryo-EM structures of the DCAF15-DDB1-DDA1-drug-RRM2 assembly (PMID:31819272, PMID:31686031, PMID:31693891). RBM23 degradation alone does not account for the widespread intron retention, exon skipping, and gene-expression changes produced by these compounds, which are instead attributable to RBM39 degradation (PMID:31693891). Beyond (PMID:15694343), (PMID:31819272, PMID:31686031, PMID:31693891), and (PMID:31693891), the broader transcriptomic targets and direct splicing substrates of RBM23 have not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2005 Medium

    Established that RBM23 is bifunctional, separating its role as a steroid hormone receptor coactivator from its role in alternative splicing into distinct protein domains.

    Evidence Luciferase reporter, splicing minigene, siRNA knockdown, and mutational analysis

    PMID:15694343

    Open questions at the time
    • Direct RNA substrates and splicing targets of RBM23 not defined
    • Most data derived for the CAPERalpha paralog with CAPERbeta as supporting evidence
    • No structural basis for either function resolved here
  2. 2019 High

    Defined how aryl sulfonamides convert the RBM23 RRM2 domain into a drug-induced degron, answering how a small molecule glues RBM23 to an E3 ligase for degradation.

    Evidence 2.3 Å crystal structure and cryo-EM of the DCAF15-DDB1-DDA1-drug-RRM2 complex with domain mapping, random mutagenesis, and degradation assays in HCT116 cells, replicated across three labs

    PMID:31686031 PMID:31693891 PMID:31819272

    Open questions at the time
    • Physiological (drug-independent) regulators of RBM23 stability unknown
    • Functional consequence of RBM23 loss in normal cells not addressed
    • Whether the RRM2 degron has an endogenous ligand unresolved
  3. 2019 Medium

    Determined that RBM23 degradation is not the driver of the splicing and expression changes caused by indisulam, isolating RBM39 as the functionally relevant target.

    Evidence Selective degradation, siRNA knockdown, and RNA-seq splicing analysis in HCT116 cells

    PMID:31693891

    Open questions at the time
    • Endogenous splicing program controlled by RBM23 not mapped
    • Single-lab finding in one cell line
    • Possible context-dependent RBM23 splicing roles untested
  4. 2021 Low

    Linked RBM23 to NF-κB signaling and tumor angiogenesis, indicating a role in regulating p65 and proangiogenic cytokine output.

    Evidence siRNA knockdown in HCC cell lines with tube formation assay, nuclear fractionation, immunoblotting, and qRT-PCR

    PMID:33791378

    Open questions at the time
    • No direct biochemical interaction between RBM23 and p65 established
    • Single lab, single knockdown approach with limited mechanistic depth
    • Mechanism by which RBM23 controls p65 mRNA levels unknown
  5. 2026 Low

    Implicated RBM23 in metabolic and redox control of colon cancer cells through effects on c-Myc stability, glycolysis, and ferroptosis.

    Evidence siRNA knockdown, cycloheximide chase, nuclear fractionation, immunofluorescence, glucose uptake, and ROS/lipid peroxidation staining

    PMID:41857570

    Open questions at the time
    • No direct biochemical interaction between RBM23 and c-Myc shown
    • Mechanism inferred from downstream phenotypes only
    • Single lab without orthogonal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous RNA targets, splicing program, and physiological regulation of RBM23 remain undefined, as does the mechanism connecting it to NF-κB and c-Myc.
  • No transcriptome-wide direct target map for RBM23
  • No structural basis for its coactivator or splicing functions
  • Cancer phenotypes lack direct biochemical mechanism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 1
Partners
DCAF15RBM39
Complex memberships
CRL4-DCAF15 E3 ubiquitin ligase (drug-induced neosubstrate)

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 RBM23 (CAPERbeta) functions as a coactivator of steroid hormone receptors (e.g., progesterone receptor) and regulates alternative pre-mRNA splicing. Mutational analysis showed that the transcriptional coactivation and splicing functions reside in distinct, separable domains of the protein. Luciferase transcription reporter assays, alternative splicing minigene assays, siRNA knockdown, mutational analysis Molecular cell Medium 15694343
2019 RBM23 is recruited to the CRL4-DCAF15 E3 ubiquitin ligase complex via its RRM2 (RNA recognition motif 2) domain in the presence of aryl sulfonamide drugs (indisulam, E7820, tasisulam), leading to RBM23 ubiquitination and proteasomal degradation. The RRM2 degron motif is shared exclusively between RBM23 and RBM39 among human proteins. Crystal structure (2.3 Å) and cryo-EM structure of DCAF15-DDB1-DDA1-drug-RBM39(RRM2) complex; domain mapping; random mutagenesis; RBM39/RBM23 degradation assays in HCT116 cells; RBM39 point mutants validated structural model Nature chemical biology / Cell reports High 31686031 31693891 31819272
2019 Degradation of RBM23 by aryl sulfonamides does not account for the widespread splicing changes (intron retention, exon skipping) and gene expression alterations caused by indisulam; these effects are attributable solely to RBM39 degradation. siRNA knockdown, RNA-seq splicing analysis, selective degradation in HCT116 cells Cell reports Medium 31693891
2021 RBM23 knockdown in HCC cells inhibits NF-κB signaling by increasing p65 mRNA levels and enhancing nuclear accumulation of p65, leading to reduced expression of proangiogenic cytokines and impaired tube formation by endothelial cells. siRNA knockdown in HCC cell lines, tube formation assay, nuclear fractionation, immunoblotting, qRT-PCR BioMed research international Low 33791378
2026 RBM23 knockdown in colon cancer cells reduces c-Myc protein stability (assessed by cycloheximide chase), decreases glycolytic enzyme expression and glucose uptake, elevates ROS, and triggers ferroptosis via regulation of GPX4 and KEAP1. RBM23 localizes to the nucleus (confirmed by immunofluorescence and nuclear fractionation). siRNA knockdown, cycloheximide chase assay, nuclear fractionation, immunofluorescence, CCK-8/colony formation assays, C11-BODIPY and DCFH-DA staining, Western blotting, glucose uptake assay Cancer cell international Low 41857570

Source papers

Stage 0 corpus · 14 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex. Nature chemical biology 188 31819272
2005 Steroid hormone receptor coactivation and alternative RNA splicing by U2AF65-related proteins CAPERalpha and CAPERbeta. Molecular cell 168 15694343
2019 Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nature chemical biology 166 31686031
2019 Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15. Cell reports 93 31693891
2023 E3-Specific Degrader Discovery by Dynamic Tracing of Substrate Receptor Abundance. Journal of the American Chemical Society 35 36602777
2022 A new cell-free therapeutic strategy for liver regeneration: Human placental mesenchymal stem cell-derived extracellular vesicles. Journal of tissue engineering 14 36313857
2021 RBM23 Drives Hepatocellular Carcinoma by Activating NF-κB Signaling Pathway. BioMed research international 14 33791378
2015 Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines. Cell biology international 13 26010766
2020 Aryl Sulfonamides Induce Degradation of Aryl Hydrocarbon Receptor Nuclear Translocator through CRL4DCAF15 E3 Ligase. Molecules and cells 8 33168788
2020 Improved Detection of Potentially Pleiotropic Genes in Coronary Artery Disease and Chronic Kidney Disease Using GWAS Summary Statistics. Frontiers in genetics 8 33343632
2023 CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p. Clinical science (London, England : 1979) 7 36896931
2023 Circ_RBM23 knockdown suppresses chemoresistance, proliferation, migration and invasion of sorafenib-resistant HCC cells through miR-338-3p/RAB1B axis. Pathology, research and practice 6 37075641
2026 Inhibition of RBM23 induces ferroptosis in colon cancer cells via c-Myc regulation. Cancer cell international 0 41857570
2025 Network-driven identification of indisulam neo-substrates for targeted protein degradation. Molecular omics 0 40985266

Missed literature

Know a paper Affinage missed for RBM23? Flag it for the maintainers and the community.

No submissions yet.