Affinage

RBM39

RNA-binding protein 39 · UniProt Q14498

Length
530 aa
Mass
59.4 kDa
Annotated
2026-06-10
97 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM39 (CAPERα/Hcc-1) is a multifunctional nuclear RNA-binding protein that operates both as a regulator of alternative pre-mRNA splicing and as a transcriptional coactivator (PMID:11704680, PMID:15694343, PMID:27354116). Through its tandem RRM domains it binds RNA in a structurally distinct manner—RRM1 recognizes stem-loop elements while RRM2 binds single-stranded N(G/U)NUUUG motifs—and CLIP-Seq maps its binding predominantly to sequences flanking 5' and 3' splice sites, where it controls cassette-exon and other alternative splicing events (PMID:27354116, PMID:37666821). RBM39 engages the core 3' splice site machinery through its UHM domain, which binds ULM motifs in U2AF65 and SF3b155 to promote U2 snRNP recruitment and spliceosome A-complex assembly (PMID:24795046, PMID:27050129, PMID:28193846). It autoregulates its own abundance by directing inclusion of an NMD-targeted poison exon into its own transcript (PMID:37666821, PMID:39316649). Independently, RBM39 acts as a coactivator that potentiates transactivation by ERα/ERβ, AP-1/c-Jun, progesterone receptor, NF-κB/Rel, ERRα, and YAP/TAZ, and facilitates chromatin activation via the MLL1 complex and H3K4 trimethylation, with transcriptional and splicing functions mapping to separable domains (PMID:11704680, PMID:15694343, PMID:18753212, PMID:25830341, PMID:34077726, PMID:39004623). RBM39 protein levels are tightly controlled by post-translational modification and ubiquitin signaling: c-Abl phosphorylates Y95/Y99 and CDK13 phosphorylates S117 to modulate its coactivator and mRNA-stabilizing activities, PRMT6 methylation at R92 and USP39 deubiquitination stabilize it, and RNF147 destabilizes it (PMID:27018250, PMID:39260689, PMID:40465651, PMID:41997449, PMID:31289203). RBM39 is the selective neo-substrate of aryl-sulfonamide molecular glues (indisulam, E7820, CQS), which occupy a shallow, non-conserved pocket on the CRL4 substrate receptor DCAF15 and cooperatively recruit an α-helical degron within RBM39's RRM2 domain for ubiquitination and proteasomal degradation—a property shared only with the paralog RBM23 (PMID:28437394, PMID:31819272, PMID:31686031, PMID:31693911, PMID:31693891).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 Medium

    Established RBM39 as a transcriptional coactivator, defining its first molecular function beyond a nuclear protein of unknown role.

    Evidence Yeast two-hybrid, Co-IP and luciferase reporter assays showing selective binding to c-Jun and ER ligand-binding domains and stimulation of ERα/ERβ/AP-1 transactivation

    PMID:11704680

    Open questions at the time
    • Did not address whether splicing and coactivation are linked
    • No structural basis for receptor binding
  2. 2004 Medium

    Showed RBM39 is a nuclear-matrix DNA/RNA-associated protein with helicase partners and a cell-cycle phenotype, broadening it beyond transcription.

    Evidence Nuclear fractionation, DNA-binding assays, yeast two-hybrid (BAT1, DDX39) and flow cytometry in HEK293 cells

    PMID:15338056

    Open questions at the time
    • Functional significance of DNA/S-MAR binding unresolved
    • Helicase interactions not validated reciprocally in cells
  3. 2005 High

    Demonstrated that RBM39 couples transcriptional coactivation and alternative splicing through separable domains, unifying its dual identity.

    Evidence Reporter assays, calcitonin/CGRP and VEGF minigene/endogenous splicing analyses with siRNA in a single study

    PMID:15694343

    Open questions at the time
    • Did not map RNA-binding specificity
    • Spliceosome contacts not identified
  4. 2014 High

    Provided the structural basis for RBM39's incorporation into the spliceosome by defining its UHM–ULM interactions with SF3b155.

    Evidence 1.7 Å crystal structure, ITC and Co-IP from human cell extracts

    PMID:24795046

    Open questions at the time
    • Did not establish which splicing events require this contact in vivo
  5. 2016 High

    Defined the second core spliceosomal contact (U2AF65) and mapped RBM39's genome-wide RNA binding and splicing program, establishing it as a bona fide splicing regulator near splice sites.

    Evidence Crystal/NMR structures of UHM–U2AF65, ITC, Co-IP, and CLIP-seq/RNA-seq with knockdown in MCF-7

    PMID:27050129 PMID:27354116

    Open questions at the time
    • Direct RNA-binding sequence specificity not yet structurally defined
    • U2AF65 vs SF3b155 functional division unclear
  6. 2017 High

    Identified RBM39 as the cellular target of anticancer aryl-sulfonamides via DCAF15-dependent degradation, transforming it into a pharmacologically actionable node.

    Evidence CRISPR-Cas9 DCAF15 knockout, RBM39 point mutagenesis, viability assays and western blot across multiple sulfonamides

    PMID:28437394

    Open questions at the time
    • Atomic mechanism of glue-induced recruitment not yet resolved
    • Degron location undefined at the time
  7. 2019 High

    Resolved at atomic and near-atomic resolution how aryl-sulfonamides act as molecular glues, defining the RRM2 α-helical degron and the cooperative, non-conserved DCAF15 pocket recruiting RBM39 (and only RBM23).

    Evidence X-ray (2.3 Å, 1.7 Å) and cryo-EM (4.4 Å) structures, kinetic binding analysis, domain mapping, ubiquitination assays and RNA-seq

    PMID:31686031 PMID:31693891 PMID:31693911 PMID:31819272

    Open questions at the time
    • Why only RBM39/RBM23 carry a glue-competent degron not generalized
    • N-terminal ubiquitination site context vs degron geometry not fully reconciled
  8. 2021 Medium

    Linked RBM39 coactivation to chromatin modification, showing it recruits the MLL1 complex to drive H3K4me3 at oncogenic loci.

    Evidence Co-IP, ChIP-seq, domain deletion and cell-penetrating dominant-negative RRM3 peptide in breast cancer cells

    PMID:34077726

    Open questions at the time
    • Single-lab; direct MLL1 contact surface not structurally defined
    • Genome-wide MLL1 co-occupancy with RBM39 limited
  9. 2023 High

    Defined RBM39's intrinsic RNA-recognition code and the structural mechanism of its poison-exon autoregulation, explaining how it tunes its own levels.

    Evidence NMR solution structures of RRM1/RRM2 bound to RNA, minigene splicing assays and mutagenesis

    PMID:37666821

    Open questions at the time
    • How RRM3/RS domain stabilizes U2 snRNP not structurally resolved
  10. 2023 High

    Connected RBM39 to nutrient sensing and oncogenic metabolic reprogramming, showing arginine directly binds RBM39 to regulate metabolic gene expression.

    Evidence Biochemical arginine-binding assays, metabolomics, RNA-seq, genetic models in murine and patient HCC

    PMID:37804830

    Open questions at the time
    • Arginine-binding surface on RBM39 not mapped
    • Whether sensing alters splicing vs coactivation unclear
  11. 2024 Medium

    Mapped the upstream ubiquitin/modification network controlling RBM39 stability beyond the sulfonamide axis, identifying USP39, PRMT6 and CDK kinases as regulators of its abundance.

    Evidence AP-MS/Co-IP and ubiquitination assays (USP39), MS-identified methylation/phosphosites with mutagenesis and rescue (PRMT6 R92, CDK13 S117), and CMGC/CDK9 inhibition driving poison-exon NMD

    PMID:39260689 PMID:39316649 PMID:40465651 PMID:41997449

    Open questions at the time
    • Each regulator validated in a single lab/context
    • Interplay between competing modifications not integrated
    • RNF147 ligase mechanism not structurally defined
  12. 2025 Medium

    Extended RBM39 function to mRNA stabilization and decay scaffolding, showing it binds specific 3'-UTRs to stabilize DNA-repair transcripts and assembles an m6A-dependent decay complex.

    Evidence RIP-qPCR, motif mutagenesis and actinomycin D stability assays (FANCD2, OGG1, RAD50) and Co-IP/RNA decay assays for a YTHDC1–DDX5 tripartite complex on HIV-1 Tat RNA

    PMID:40364450 PMID:40752539 PMID:41218081 PMID:41997449

    Open questions at the time
    • Whether stabilization and degradation use the same RRM contacts unclear
    • Determinants of stabilize-vs-decay outcome unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RBM39 integrates its splicing, transcriptional coactivation, mRNA-stability and metabolic-sensing functions into a unified regulatory logic—and how its post-translational modification network biases between these outputs—remains unresolved.
  • No structure of full-length RBM39 with multiple partners
  • No unifying model linking modification state to functional choice
  • Many downstream target events validated only in single cancer contexts

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2 R-HSA-8953854 Metabolism of RNA 2
Partners
C-ABLC-JUNDCAF15DDX5SF3B1 (SF3B155)U2AF65USP39YTHDC1
Complex memberships
CRL4-DCAF15 E3 ligase (neo-substrate)MLL1 complexRBM39-YTHDC1-DDX5 RNA decay complexspliceosome (U2 snRNP-associated)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 Anticancer sulfonamides (E7820, indisulam, CQS) induce proteasomal degradation of RBM39 (CAPERα) via CRL4-DCAF15-mediated ubiquitination. CRISPR-Cas9 knockout of DCAF15 and a single amino acid substitution in RBM39 conferred resistance to sulfonamide-induced RBM39 degradation and cell-growth inhibition. CRISPR-Cas9 knockout, site-directed mutagenesis, cell viability assays, western blot Nature chemical biology High 28437394
2019 Crystal structure of the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex at 2.3 Å resolution revealed that DCAF15 embraces the RBM39 RRM2 domain largely via non-polar interactions, with indisulam binding between DCAF15 and RBM39(RRM2) as a molecular glue. An α-helical degron motif in RBM39 RRM2 was defined; only RBM23 and RBM39 share this degron and are degraded by indisulam. X-ray crystallography (2.3 Å), RBM39 point mutant studies, indisulam analog studies, mass spectrometry of indisulam-treated HCT116 cells Nature chemical biology High 31819272
2019 Cryo-EM structure (4.4 Å) of DDB1-DCAF15-DDA1 bound to RBM39 and E7820 showed DCAF15 adopts a new fold stabilized by DDA1, and extensive protein-protein contacts between the ligase and RBM39 compensate for low-affinity aryl-sulfonamide–DCAF15 interactions. Aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively recruit RBM39 and RBM23. Cryo-EM (4.4 Å), X-ray crystallography of subcomplexes, biochemical reconstitution Nature chemical biology High 31686031
2019 Crystal structure of DDA1-DDB1-DCAF15 in complex with E7820 and RBM39 RRM2 domain showed E7820 packs in a shallow pocket on DCAF15 and the resulting modified interface binds RBM39 through the α1 helix of RRM2. Kinetic analysis revealed that aryl sulfonamide and RBM39 bind to DCAF15 in a synergistic (cooperative) manner. X-ray crystallography, kinetic binding analysis Structure High 31693911
2019 Domain mapping and mutagenesis identified that RBM39 is recruited to DCAF15 through its RRM2 domain and is ubiquitinated on its N terminus upon indisulam treatment. DCAF15 mutations Q232 or D475 prevent RBM39 recruitment. RBM23 is also recruited and degraded via its RRM2 domain. Indisulam-induced transcriptional and splicing changes (>3,000 genes, intron retention and exon skipping) are attributable to RBM39 loss, not RBM23. Domain mapping, random mutagenesis, ubiquitination assays, RNA-seq Cell reports High 31693891
2001 RBM39 (CAPER) was identified as a nuclear coactivator that selectively binds c-Jun (AP-1 component) and estradiol-bound ligand binding domains of ERα and ERβ, and stimulates transactivation by ERα, ERβ, and AP-1 in cotransfection assays. CAPER interaction was identified via its interaction with the general coactivator ASC-2. Yeast two-hybrid screen, co-immunoprecipitation, luciferase transcription reporter assays The Journal of biological chemistry Medium 11704680
2005 RBM39 (CAPERα) coactivates progesterone receptor-mediated transcription and alters alternative splicing of a calcitonin/CGRP minigene in a hormone-dependent manner. siRNA knockdown of CAPERα affected VEGF isoform splicing. Transcriptional and splicing functions map to distinct, separable domains of the protein. Luciferase transcription reporter assays, minigene splicing assays, siRNA knockdown, RT-PCR Molecular cell High 15694343
2014 The CAPERα UHM domain interacts with SF3b155 ULM motifs (at 1.7 Å crystal structure). Isothermal titration calorimetry showed high-affinity interaction depends on an intrinsically unstructured SF3b155 domain with seven ULM-like motifs. SF3b155 was identified as the relevant ULM-containing partner of full-length CAPERα in human cell extracts. X-ray crystallography (1.7 Å), isothermal titration calorimetry, co-immunoprecipitation from cell extracts The Journal of biological chemistry High 24795046
2016 Crystal and NMR structures of the RBM39 UHM domain and its complex with U2AF65-ULM were solved. The RBM39-U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, isothermal titration calorimetry, and NMR chemical shift perturbation experiments with purified proteins. X-ray crystallography, solution NMR, co-immunoprecipitation, isothermal titration calorimetry Acta crystallographica Section D High 27050129
2016 Genome-wide CLIP-Seq mapping showed RBM39 binding sites are mainly proximal to 5' and 3' splice sites. RNA-seq of RBM39-knockdown MCF-7 cells identified hundreds of alternative splicing events (predominantly cassette exons) regulated by RBM39, with ~20% of events co-regulated with U2AF65. CLIP-Seq, RNA-seq, siRNA knockdown Biochimica et biophysica acta High 27354116
2017 During terminal erythropoiesis, RBM39 associates in a complex with TIA1 and Pcbp1 to activate the protein 4.1R exon 16 3' splice site. This complex interacts with U2AF65 and SF3b155 and promotes U2 snRNP recruitment to the branch point and spliceosome A complex formation. Co-immunoprecipitation, splicing reporter assays, siRNA knockdown, UV cross-linking Molecular and cellular biology Medium 28193846
2008 CAPERα interacts with the transcription activation domain (TAD) of v-Rel and synergizes v-Rel-mediated transactivation. A dominant-negative mutant of CAPERα enhanced v-Rel-mediated lymphocyte transformation, and siRNA knockdown of CAPERα in v-Rel-transformed lymphocytes enhanced colony formation, identifying CAPERα as a transcriptional coregulator that modulates Rel/NF-κB oncogenic activity. Co-immunoprecipitation, luciferase reporter assays, dominant-negative overexpression, siRNA knockdown, soft agar colony assay Journal of virology Medium 18753212
2015 RBM39 (CAPER) acts as a transcriptional coactivator for ERR-α–mediated Gabpa transcription to drive mitochondrial gene expression and glucose-dependent respiration. CAPER is also a coactivator for NF-κB regulating c-Myc in stress responses. CAPER is required for anaplerotic carbon flux into TCA cycles. These functions are conserved in C. elegans where CAPER loss impairs lifespan and reproduction. siRNA knockdown, luciferase reporter assays, metabolic flux analysis (isotope tracing), C. elegans genetic studies, ATP measurement PLoS genetics Medium 25830341
2016 RBM39 interacts with the non-receptor tyrosine kinase c-Abl through c-Abl SH2 and SH3 domains. c-Abl phosphorylates RBM39 at Y95 and Y99 (identified by LC/MS/MS and mutational analysis), and c-Abl enhances RBM39 transcriptional coactivation activity for ERα and PRβ in a kinase-dependent manner. Co-immunoprecipitation, LC/MS/MS phosphoproteomics, site-directed mutagenesis, luciferase reporter assays Biochemical and biophysical research communications Medium 27018250
2021 RBM39 functions as a master transcriptional regulator that interacts with the MLL1 complex to facilitate chromatin binding and H3K4 trimethylation in breast cancer cells. The RRM3 domain of RBM39 acts as a dominant-negative, disrupting the RBM39/MLL1 complex and reducing H3K4me3 and expression of target oncogenic genes. Co-immunoprecipitation, ChIP-seq, domain deletion/mutagenesis, cell-penetrating peptide experiments Cell reports Medium 34077726
2019 The lncRNA DARS-AS1 binds RBM39, impeding its interaction with the E3 ubiquitin ligase RNF147, thereby preventing RBM39 proteasomal degradation. This stabilization of RBM39 maintains mTOR signaling in myeloma cells. RNA immunoprecipitation, co-immunoprecipitation, siRNA/shRNA knockdown, ubiquitination assays, in vivo xenograft Haematologica Medium 31289203
2023 NMR solution structures of RBM39 RRM1 and RRM2 bound to their respective RNA targets were determined: RRM1 recognizes RNA stem loops whereas RRM2 binds specifically to single-stranded N(G/U)NUUUG sequences. RBM39 autoregulates its own expression via inclusion of a poison exon into its pre-mRNA, with RRM2 selecting the 3' splice site of the poison exon and the RRM3 and RS domain stabilizing U2 snRNP at the branchpoint. NMR spectroscopy (solution structures), minigene splicing assays, mutagenesis of cis-acting elements, siRNA knockdown Nature communications High 37666821
2023 Arginine directly binds RBM39 protein to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop. High arginine levels in hepatocellular carcinoma drive oncogenic metabolic reprogramming via RBM39. Biochemical binding assays (arginine-RBM39 interaction), RNA-seq, metabolomics, genetic knockdown/overexpression, mouse HCC models Cell High 37804830
2022 In response to cisplatin (genotoxic stress), c-Jun interacts with RBM39 and prevents RBM39 binding to pre-mRNA, thereby reprogramming alternative splicing genome-wide. This c-Jun–RBM39 interaction drives production of a short COASY isoform lacking exons 4 and 5 that impairs mitochondrial function and decreases cisplatin sensitivity. Co-immunoprecipitation, RNA-seq, RNA immunoprecipitation, siRNA knockdown, minigene splicing assays Nucleic acids research Medium 36477312
2004 RBM39 (Hcc-1) localizes to the nuclear matrix and binds both double-stranded and single-stranded DNA (higher affinity for ssDNA) and scaffold/matrix attachment region (S/MAR) DNA. Two DEAD-box RNA helicases, BAT1 and DDX39, were identified as RBM39-interacting proteins by yeast two-hybrid. Overexpression of Hcc-1 caused G2/M accumulation and slower growth in HEK293 cells. Nuclear fractionation, DNA binding assays, yeast two-hybrid, cell cycle analysis (flow cytometry), overexpression Cellular and molecular life sciences Medium 15338056
2024 USP39 is a deubiquitinating enzyme that interacts with RBM39 and co-localizes in the nucleus. USP39 reduces K48-linked polyubiquitin chains on RBM39, enhancing its stability and preventing proteasomal degradation. Affinity purification-mass spectrometry, co-immunoprecipitation, ubiquitination assays, shRNA knockdown, overexpression The Journal of biological chemistry Medium 39260689
2016 siRNA knockdown of RBM39 in mouse C2C12 cells increased BMP4-dependent transcription. Transcriptome-wide RNA-seq revealed that RBM39 knockdown altered Sin3b exon usage, shifting expression from the long isoform (which recruits HDACs) to the short isoform. BMP4 induced a shift toward the long SIN3B isoform that was prevented by RBM39 knockdown, constituting a negative autoregulatory loop of BMP signaling through RBM39-regulated splicing. siRNA screen, siRNA knockdown, luciferase reporter, RNA-seq, RT-PCR for isoforms Scientific reports Medium 27324164
2024 MORC2 binds the RRM1 domain of RBM39, and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, causing a splicing switch from CDK5RAP2-L to CDK5RAP2-S. CDK5RAP2-S promotes EMT and metastasis by recruiting PHD finger protein 8 to the Slug promoter to remove repressive histone marks. Co-immunoprecipitation, RNA immunoprecipitation, minigene splicing assay, domain mapping, in vitro/in vivo functional studies Cell death & disease Medium 39048555
2025 PRMT6 methylates RBM39 at R92. This methylation inhibits indisulam-induced ubiquitination and proteasomal degradation of RBM39, thereby increasing RBM39 protein levels and conferring resistance to indisulam in NSCLC. Inhibiting PRMT6 or mutating R92 restores indisulam sensitivity. Mass spectrometry (phospho/methylo-proteomics), site-directed mutagenesis, ubiquitination assays, PRMT6 inhibitor treatment, xenograft models PLoS biology Medium 40465651
2024 YAP/TAZ interact with RBM39 (identified by proteome analysis) and RBM39 promotes YAP/TAZ transcriptional activity. YAP/TAZ hyperactivation delays indisulam-induced RBM39 degradation, restoring integrin/collagen expression and activating FAK to confer resistance against indisulam. Proteome analysis, co-immunoprecipitation, luciferase reporter assays, western blot, in vivo xenograft Oncogenesis Medium 39004623
2025 RBM39 scaffolds an m6A-dependent RNA decay complex by recruiting the m6A reader YTHDC1 and RNA helicase DDX5, forming a tripartite complex that accelerates Tat (HIV-1) RNA decay and enforces viral quiescence. Genetic or pharmacological degradation of RBM39 reactivates latent HIV-1. Proteomics, co-immunoprecipitation, RNA decay assays, RBM39 knockdown/degradation, latency reactivation assays PLoS biology Medium 41218081
2021 In PRRSV-infected cells, RBM39 alters phosphorylation of c-Jun to inhibit the AP-1 pathway, promoting viral proliferation. RBM39 undergoes nucleocytoplasmic translocation from nucleus to cytoplasm. The three RRM domains of RBM39 are required for supporting PRRSV proliferation. RBM39 directly binds several PRRSV RNA segments (nsp4, nsp5, nsp7, nsp10-12, M and N genes). siRNA knockdown, phosphorylation assays, co-immunoprecipitation, RNA immunoprecipitation, confocal microscopy, viral replication assays Frontiers in immunology Medium 34079549
2024 CMGC kinase inhibition (including DYRK1A) or CDK9 inhibition disrupts cotranscriptional splicing by altering SF3B1 and Pol II association and changing Pol II pausing, leading to inclusion of a poison exon in RBM39 pre-mRNA, which is recognized by NMD for degradation. This reduces RBM39 protein levels and inhibits B-ALL growth. Kinase inhibitor treatment, CRISPR knockout, RNA-seq, ChIP/CUT&RUN, NMD assays Blood Medium 39316649
2026 CDK13 directly phosphorylates RBM39 at serine 117 (identified by phosphoproteomic analysis). This phosphorylation enhances RBM39's ability to bind and stabilize RAD50 mRNA, increasing RAD50 protein levels and promoting DNA damage repair, thereby driving cisplatin resistance in endometrial cancer. Phosphoproteomics (LC-MS/MS), site-directed mutagenesis (S117A), RIP assays, mRNA stability assays (actinomycin D), in vivo xenograft The Journal of biological chemistry Medium 41997449
2025 RBM39 regulates alternative splicing of EZH2 pre-mRNA; RBM39 depletion suppresses EZH2 expression. RBM39-regulated EZH2 controls WNT7B/β-catenin activity, establishing an RBM39-EZH2-β-catenin signaling axis in cholangiocarcinoma. CRISPR/Cas9 and shRNA depletion, RNA-seq splicing analysis, western blot, in vivo xenograft Cellular and molecular gastroenterology and hepatology Low 39278404
2025 RBM39 binds the 3'-UTR of FANCD2 mRNA (validated by RIP-qPCR and motif mutagenesis) and extends FANCD2 mRNA half-life (actinomycin D assay), thereby stabilizing FANCD2 protein and promoting DNA repair in esophageal cancer. RNA immunoprecipitation (RIP-qPCR), motif mutagenesis, mRNA stability assay (actinomycin D), FANCD2 overexpression rescue Cellular signalling Medium 40752539
2025 RBM39 binds RFX1 pre-mRNA (identified by RIP-seq) and regulates alternative splicing of RFX1 exon 2. Skipping of exon 2 produces an N-terminal truncated RFX1 lacking transcriptional repression activity on oncogenic collagen genes, leading to activation of the FAK/PI3K/AKT signaling pathway in HCC. RIP-seq, minigene splicing assay, RT-PCR, CRISPR/shRNA knockdown, in vivo xenograft Oncogene Medium 40033026
2025 RBM39 depletion reduced expression of IRF3, RIG-I, and MDA5 (transcription and/or splicing affected), as well as IFN receptor subunits IFNAR and STAT1/2, impairing TLR3, RIG-I/MDA5, and type I/III IFN responses in hepatocytes. A genome-wide CRISPR/Cas9 screen identified RBM39 as a required factor for TLR3 pathway activation. Genome-wide CRISPR/Cas9 screen, siRNA knockdown, indisulam treatment, RNA-seq, mass spectrometry Frontiers in immunology Medium 40330464
2025 RBM39 promotes base excision repair (BER) in HCC by binding OGG1 mRNA and stabilizing it, increasing OGG1 expression and BER efficiency under oxidative stress. This was demonstrated using a BER reporter assay and RBM39 knockdown/degradation experiments. BER reporter assay, RNA immunoprecipitation, mRNA stability assay, siRNA knockdown, indisulam treatment, xenograft model Cell proliferation Low 40364450
2025 RBM39 regulates MEK5 pre-mRNA splicing; RBM39 knockdown causes aberrant MEK5 isoforms with exon loss that are non-functional and prone to proteasomal degradation. Full-length MEK5 is required for multiple myeloma cell survival. shRNA knockdown, RNA-seq splicing analysis, RT-PCR isoform analysis, western blot, in vivo xenograft Blood advances Low 40048740
2025 Rbm39 enhances hepatocyte nuclear factor 4α (Hnf4α) transcriptional activity to upregulate Apob transcription, while suppressing Fabp4 transcription through regulation of alternative splicing of Hif-1α, thereby maintaining hepatic lipid homeostasis. AAV-mediated Rbm39 overexpression/knockdown, RNA-seq, dual-luciferase reporter assays, alternative splicing analysis, RT-PCR Biochimica et biophysica acta Molecular basis of disease Low 40147697
2011 CAPER-α expression correlates inversely with the VEGF165/VEGF189 mRNA ratio in Ewing sarcoma cells. Transfection of CAPER-α cDNA or siRNA knockdown altered VEGF isoform splicing (VEGF189 vs VEGF165). CAPER-α expression was regulated by EWS/FLI-1 through a protein-protein interaction. cDNA transfection, siRNA knockdown, RT-PCR isoform analysis, co-immunoprecipitation (protein-protein interaction), in vivo tumor growth assay Cancer Medium 22009261

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Selective degradation of splicing factor CAPERα by anticancer sulfonamides. Nature chemical biology 302 28437394
2023 Arginine reprograms metabolism in liver cancer via RBM39. Cell 226 37804830
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 Structural Basis and Kinetic Pathway of RBM39 Recruitment to DCAF15 by a Sulfonamide Molecular Glue E7820. Structure (London, England : 1993) 131 31693911
1996 HCC-1, a novel chemokine from human plasma. The Journal of experimental medicine 113 8551235
2019 Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15. Cell reports 93 31693891
2001 Molecular cloning and characterization of CAPER, a novel coactivator of activating protein-1 and estrogen receptors. The Journal of biological chemistry 93 11704680
2021 RNA-binding motif protein 39 (RBM39): An emerging cancer target. British journal of pharmacology 73 33238031
2019 Hypoxia-induced long non-coding RNA DARS-AS1 regulates RBM39 stability to promote myeloma malignancy. Haematologica 61 31289203
2021 Targeting the spliceosome through RBM39 degradation results in exceptional responses in high-risk neuroblastoma models. Science advances 56 34788094
2014 Cancer-relevant splicing factor CAPERα engages the essential splicing factor SF3b155 in a specific ternary complex. The Journal of biological chemistry 55 24795046
2016 Global regulation of alternative RNA splicing by the SR-rich protein RBM39. Biochimica et biophysica acta 53 27354116
1998 Identification of C-C chemokine receptor 1 (CCR1) as the monocyte hemofiltrate C-C chemokine (HCC)-1 receptor. The Journal of experimental medicine 51 9687537
2011 CAPER-α alternative splicing regulates the expression of vascular endothelial growth factor₁₆₅ in Ewing sarcoma cells. Cancer 46 22009261
2005 Microbiological study of lactic acid fermentation of Caper berries by molecular and culture-dependent methods. Applied and environmental microbiology 45 16332762
2016 UHM-ULM interactions in the RBM39-U2AF65 splicing-factor complex. Acta crystallographica. Section D, Structural biology 44 27050129
2021 Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells. Nature communications 43 34257283
2017 Venezuelan Equine Encephalitis Virus Capsid-The Clever Caper. Viruses 43 28961161
2011 The anticarcinogenic potential of essential oil and aqueous infusion from caper (Capparis spinosa L.). Food chemistry 43 26434289
2008 CAPERalpha is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-kappaB oncoprotein v-Rel. Journal of virology 40 18753212
2008 A protein with antiproliferative, antifungal and HIV-1 reverse transcriptase inhibitory activities from caper (Capparis spinosa) seeds. Phytomedicine : international journal of phytotherapy and phytopharmacology 40 19019643
2015 CAPER is vital for energy and redox homeostasis by integrating glucose-induced mitochondrial functions via ERR-α-Gabpa and stress-induced adaptive responses via NF-κB-cMYC. PLoS genetics 39 25830341
2012 CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression. Cellular oncology (Dordrecht, Netherlands) 32 22711543
2023 Molecular basis of RNA-binding and autoregulation by the cancer-associated splicing factor RBM39. Nature communications 31 37666821
1999 Organization of the chemokine gene cluster on human chromosome 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, HCC-1, LEC, and RANTES. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 31 10213461
2004 Hcc-1 is a novel component of the nuclear matrix with growth inhibitory function. Cellular and molecular life sciences : CMLS 30 15338056
2023 Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma. Cell reports 29 37858464
2018 Impact of different geographical locations on varying profile of bioactives and associated functionalities of caper (Capparis spinosa L.). Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 28 29751072
2014 CAPER, a novel regulator of human breast cancer progression. Cell cycle (Georgetown, Tex.) 28 24621503
2014 Overexpression of HCC1/CAPERα may play a role in lung cancer carcinogenesis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 28 24643682
2016 Innate immune and growth promoting responses to caper (Capparis spinosa) extract in rainbow trout (Oncorhynchus mykiss). Fish & shellfish immunology 26 27546553
2021 RBM39 Alters Phosphorylation of c-Jun and Binds to Viral RNA to Promote PRRSV Proliferation. Frontiers in immunology 23 34079549
2017 Protein 4.1R Exon 16 3' Splice Site Activation Requires Coordination among TIA1, Pcbp1, and RBM39 during Terminal Erythropoiesis. Molecular and cellular biology 22 28193846
2021 Inhibiting an RBM39/MLL1 epigenomic regulatory complex with dominant-negative peptides disrupts cancer cell transcription and proliferation. Cell reports 21 34077726
2012 CAPER: a chromosome-assembled human proteome browsER. Journal of proteome research 20 23256906
2023 The cancer-testis lncRNA LINC01977 promotes HCC progression by interacting with RBM39 to prevent Notch2 ubiquitination. Cell death discovery 19 37198207
2020 Development of CAPER peptides for the treatment of triple negative breast cancer. Cell cycle (Georgetown, Tex.) 18 31931653
2017 The RNA-binding protein caper is required for sensory neuron development in Drosophila melanogaster. Developmental dynamics : an official publication of the American Association of Anatomists 17 28543982
2024 A molecular glue RBM39-degrader induces synthetic lethality in cancer cells with homologous recombination repair deficiency. NPJ precision oncology 16 38789724
2016 Functional interaction between nonreceptor tyrosine kinase c-Abl and SR-Rich protein RBM39. Biochemical and biophysical research communications 16 27018250
2024 Targeting RBM39 through indisulam induced mis-splicing of mRNA to exert anti-cancer effects in T-cell acute lymphoblastic leukemia. Journal of experimental & clinical cancer research : CR 13 39044280
2024 MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer. Cell death & disease 13 39048555
2024 HCC-1 Accelerates Atherosclerosis by Inducing Endothelial Cell and Macrophage Pyroptosis and Serves as an Early Diagnostic Biomarker. Arteriosclerosis, thrombosis, and vascular biology 12 39087347
2023 Regulatory role of RBM39 in acute myeloid leukemia: Mediation through the PI3K/AKT pathway. Biochimica et biophysica acta. Molecular cell research 12 37852323
2021 Biotreatment efficiency, hydrolytic potential and bacterial community dynamics in an immobilized cell bioreactor treating caper processing wastewater under highly saline conditions. Bioresource technology 12 33454565
2022 The transcription factor c-Jun inhibits RBM39 to reprogram pre-mRNA splicing during genotoxic stress. Nucleic acids research 11 36477312
2016 Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma. Oncotarget 11 26934653
2016 Negative autoregulation of BMP dependent transcription by SIN3B splicing reveals a role for RBM39. Scientific reports 11 27324164
2024 Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39. The Journal of biological chemistry 10 39260689
2018 CAPER as a therapeutic target for triple negative breast cancer. Oncotarget 10 30100993
2021 The conserved alternative splicing factor caper regulates neuromuscular phenotypes during development and aging. Developmental biology 8 33508255
2013 CAPER 2.0: an interactive, configurable, and extensible workflow-based platform to analyze data sets from the Chromosome-centric Human Proteome Project. Journal of proteome research 8 24261964
2024 RBM39 Enhances Cholangiocarcinoma Growth Through EZH2-mediated WNT7B/β-catenin Pathway. Cellular and molecular gastroenterology and hepatology 7 39278404
2025 RBM39 promotes hepatocarcinogenesis by regulating RFX1's alternative splicing and subsequent activation of integrin signaling pathway. Oncogene 6 40033026
2024 YAP/TAZ interacts with RBM39 to confer resistance against indisulam. Oncogenesis 6 39004623
2023 RBM39: A druggable metabolic sensor linking RNA splicing, transcriptional regulation, and metabolic reprogramming in cancer. Molecular cell 6 38065060
2025 RNA-binding motif protein RBM39 enhances the proliferation of gastric cancer cells by facilitating an oncogenic splicing switch in MRPL33. Acta pharmacologica Sinica 5 39753980
2024 Disruption of cotranscriptional splicing suggests RBM39 is a therapeutic target in acute lymphoblastic leukemia. Blood 5 39316649
2023 Overlaid Transcriptional and Proteome Analyses Identify Mitotic Kinesins as Important Targets of Arylsulfonamide-Mediated RBM39 Degradation. Molecular cancer research : MCR 5 37255411
2019 No Matter How You Splice It, RBM39 Inhibition Targets Spliceosome Mutant AML. Cancer cell 5 30889374
2015 CAPER 3.0: A Scalable Cloud-Based System for Data-Intensive Analysis of Chromosome-Centric Human Proteome Project Data Sets. Journal of proteome research 5 25794139
2015 Genetic diversity and host alternation of the egg parasitoid Ooencyrtus pityocampae between the pine processionary moth and the caper bug. PloS one 5 25856082
2025 RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity. Nature communications 4 40962798
2024 Targeting RBM39 suppresses tumor growth and sensitizes osteosarcoma cells to cisplatin. Oncogene 4 39633066
2023 Prophylactic effects of dietary caper (Capparis spinosa) extracts on the control of Streptococcus agalactiae infection, growth, immune-antioxidant, and inflammation cytokine responses of Nile tilapia fingerlings. Fish & shellfish immunology 4 37777101
2025 RBM39 Promotes Base Excision Repair to Facilitate the Progression of HCC by Stabilising OGG1 mRNA. Cell proliferation 3 40364450
2025 Methylation of RBM39 by PRMT6 enhances resistance to Indisulam in non-small cell lung cancer by promoting alternative splicing of proto-oncogenes. PLoS biology 3 40465651
2024 LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis. Molecular and cellular biochemistry 3 38472681
2024 Recent advances in anticancer mechanisms of molecular glue degraders: focus on RBM39-dgrading synthetic sulfonamide such as indisulam, E7820, tasisulam, and chloroquinoxaline sulfonamide. Genes & genomics 3 39271535
2022 Biochemical, pharmacological, and toxicological attributes of caper (Capparis ovata) flowering buds and berries pickles. Food science & nutrition 3 36514771
2025 Synthesis of an RBM39 Degrader That Downregulates CEP192 and Induces Disorganized Spindle Structures. Journal of medicinal chemistry 2 40107850
2025 Targeting RBM39 with Tasisulam enhances TRAIL-induced apoptosis through DR5 upregulation and Bcl-2 downregulation in renal cell carcinoma. Biochemical pharmacology 2 40112928
2025 RBM39 Functions as a Potential Oncogene Through the NF-κB Signaling Pathway in Colorectal Cancer Cells. Journal of Cancer 2 40302803
2024 Spatial transcriptomics identifies RBM39 as a gene associated with Gleason score progression in prostate cancer. iScience 2 39650727
2023 The identification of protein and RNA interactors of the splicing factor Caper in the adult Drosophila nervous system. Frontiers in molecular neuroscience 2 37435576
2026 A Small Indole Derivative Isolated From Caper (Capparis ovata) as an Inducer of P53-Mediated Apoptosis in Prostate Cancer: Comprehensive In Vitro and In Silico Studies. Journal of biochemical and molecular toxicology 1 41476392
2025 Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma. Blood advances 1 40048740
2025 Rbm39 ameliorates metabolic dysfunction-associated steatotic liver disease by regulating Apob and Fabp4. Biochimica et biophysica acta. Molecular basis of disease 1 40147697
2025 The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8. Cell & bioscience 1 40223119
2025 RBM39 silence suppresses esophageal cancer proliferation and metastasis via FANCD2 mRNA destabilization. Cellular signalling 1 40752539
2025 The RNA-binding protein RBM39 scaffolds an m⁶A-dependent RNA decay complex that destabilizes Tat transcripts and restricts HIV-1 reactivation. PLoS biology 1 41218081
2025 RBM39 Contributes to MGMT Maintenance in Response to Temozolomide-Induced DNA Damage. Cancers 1 41300971
2024 Theileria annulata subtelomere-encoded variable secreted protein-TA05560 interacts with bovine RNA binding motif protein 39 (RBM39). Acta tropica 1 38280638
2023 Germplasm characterization and SDS-PAGE analysis of caper (Capparis spinosa L.) from different provenances. BMC plant biology 1 38072942
2022 Roles for the RNA-Binding Protein Caper in Reproductive Output in Drosophila melanogaster. Journal of developmental biology 1 36648904
2021 Complete genome sequence of a new isolate of caper latent virus in caper. Archives of virology 1 34213637
2026 Exploiting the polypharmacology of alectinib for synergistic RNA splicing disruption with RBM39 degraders. Cell reports 0 41518614
2026 Correction: RBM39 shapes innate immunity by controlling expression of key factors of the interferon response. Frontiers in immunology 0 41668740
2026 Phosphorylation of RBM39 by CDK13 stabilizes RAD50 mRNA to drive cisplatin resistance in endometrial cancer. The Journal of biological chemistry 0 41997449
2026 Discovery and characterization of YSA64, a RBM39 degrader with in vivo efficacy and potent cellular activity in pediatric Ewing sarcoma A673. European journal of medicinal chemistry 0 42085934
2025 RBM39 shapes innate immunity by controlling the expression of key factors of the interferon response. Frontiers in immunology 0 40330464
2025 1H, 13C and 15N backbone resonance assignment of the RNA binding motif 39 (RBM39) tandem RNA recognition motifs (RRM1-2). Biomolecular NMR assignments 0 40944856
2025 Transcriptomic and epigenetic profiling of neuroblastoma states in response to RBM39 degrader. Scientific data 0 41365913
2024 RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity. bioRxiv : the preprint server for biology 0 38585889
2023 HCC1, a Polygalacturonase, Regulates Chlorophyll Degradation via the Ethylene Synthesis Pathway. Rice (New York, N.Y.) 0 38071259

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