Affinage

RBM38

RNA-binding protein 38 · UniProt Q9H0Z9

Length
239 aa
Mass
25.5 kDa
Annotated
2026-06-10
66 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM38 (RNPC1) is an RRM-domain RNA-binding protein that governs post-transcriptional gene expression—mRNA stability, alternative splicing, translation, and miRNA accessibility—within a regulatory hub centered on the p53 family and cell-cycle/senescence control (PMID:17050675, PMID:21764855, PMID:24250749). Its RRM recognizes G(U/C/A)GUG and AU/U-rich elements through two stacking phenylalanine residues and sequence-specific hydrogen bonds, as resolved by crystallography (PMID:31860021). Through these elements RBM38 stabilizes a set of growth-suppressive transcripts (p21, p73, PTEN, HuR, MIC-1) while destabilizing others (p63, MDM2, c-Myc), thereby coupling p53-family output to differentiation, growth arrest, and senescence (PMID:17050675, PMID:20457941, PMID:22710720, PMID:22371495, PMID:22508983, PMID:29052531). A central node is translational repression of p53: RBM38 uses its N-terminus to bind p53 mRNA 5'/3' UTRs and its C-terminus to bind eIF4E, blocking cap recognition; this repression is converted to activation when Ser195 phosphorylation (by GSK3 or CDK4, reversed by PPM1D) switches RBM38 from an eIF4E-interacting repressor to an eIF4G-recruiting promoter of eIF4F assembly (PMID:21764855, PMID:24142875, PMID:25823026, PMID:41154395). The same Ser195 switch governs RBM38's association with Ago2, tuning miRNA-mediated decay of targets such as p63 and survivin (PMID:30567739, PMID:33472892). The p53-RBM38 loop and the RBM38-p63 loop operate in vivo, where Rbm38 loss accelerates aging, causes hematopoietic defects and tumors, and modulates p53/p63-dependent senescence (PMID:25512531, PMID:29520104). Beyond the p53 axis, RBM38 controls alternative splicing during erythroid differentiation, regulating Protein 4.1R and Ferrochelatase to support heme biosynthesis—its loss producing microcytic anemia and an erythropoietic protoporphyria-like phenotype (PMID:24250749, PMID:40961234). The eIF4E-binding interface is druggable: a derived peptide (Pep8) and small molecule 094 dissociate RBM38 from eIF4E to relieve p53 translational repression and suppress tumor growth (PMID:30591552, PMID:36940176).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established RBM38 as a direct, isoform-specific regulator of mRNA stability, linking it to p21 and cell-cycle arrest.

    Evidence RNA binding assays plus knockdown/overexpression mRNA stability and cell-cycle analysis of RNPC1a vs RNPC1b

    PMID:17050675

    Open questions at the time
    • Mechanism distinguishing isoform a from b activity not defined
    • binding-site element on p21 3' UTR not mapped at residue level
  2. 2010 High

    Showed RBM38 acts cooperatively with HuR and can both stabilize (p21) and destabilize (p63) transcripts through its RRM, broadening its target logic.

    Evidence Reciprocal Co-IP/domain mapping with HuR, RNA-IP, EMSA, and RRM-mutant stability assays in keratinocyte differentiation

    PMID:20064878 PMID:20457941

    Open questions at the time
    • What determines whether RBM38 stabilizes versus destabilizes a given target is unresolved
    • no structural basis for HuR cooperativity
  3. 2011 High

    Defined RBM38's translational-repression mechanism—blocking eIF4E from the p53 mRNA cap—and its miRNA-gating role, embedding it in a p53 autoregulatory circuit.

    Evidence Domain-mapped Co-IP with eIF4E, polysome profiling, MEF senescence assays, and a genetic screen for RBP control of miRNA activity

    PMID:21764855 PMID:22027593

    Open questions at the time
    • Stoichiometry of RBM38-eIF4E-mRNA complex unknown
    • rules governing which miRNA target sites RBM38 occludes not generalized
  4. 2012 High

    Expanded the target network (MDM2, HuR, p73, MIC-1) and identified E2F1 as a transcriptional input, positioning RBM38 in multiple feedback loops controlling growth suppression and senescence.

    Evidence RNA-IP/EMSA stability assays with RRM mutants, KO corroboration, siRNA epistasis in MEFs, and E2F1 promoter ChIP

    PMID:22371495 PMID:22508983 PMID:22710720 PMID:22798430 PMID:23836903

    Open questions at the time
    • Hierarchy among competing targets in a single cell unclear
    • E2F1 regulation is Medium-confidence and single-lab
  5. 2013 High

    Resolved how RBM38's regulatory mode is switched and defined a splicing-activator role, with SELEX-Seq fixing a GU-rich binding motif.

    Evidence In vitro GSK3 kinase assay, phosphomimetic S195D mutants, Co-IP with eIF4E/eIF4G, and minigene/tethering splicing assays with SELEX-Seq

    PMID:24142875 PMID:24250749

    Open questions at the time
    • How Ser195 phosphorylation physically remodels the eIF4E vs eIF4G interface not structurally defined
    • splicing target repertoire incomplete
  6. 2014 High

    Provided in vivo genetic proof of the p53-Rbm38 autoregulatory loop through aging, tumor, and radiation-sensitivity phenotypes.

    Evidence Rbm38-null mice, IR challenge, and compound epistasis with p53-heterozygous mice

    PMID:25512531

    Open questions at the time
    • Tissue-specific contributions of individual targets to phenotypes not dissected
  7. 2015 Medium

    Identified PPM1D as the phosphatase reversing the Ser195 switch and extended translational control to HIF1α, defining bidirectional regulatory axes.

    Evidence In vitro dephosphorylation assay, Co-IP, RNA-IP, cap-binding assays, and reporter assays for PPM1D and HIF1α UTRs

    PMID:25622105 PMID:25823026

    Open questions at the time
    • HIF1α regulation single-lab and Medium-confidence
    • kinetics of phosphorylation/dephosphorylation cycling in vivo unknown
  8. 2017 Medium

    Embedded RBM38 in multiple cancer feedback loops (c-Myc, Snail/ZO-1, ER/PR, PTEN, ceRNA network) controlling proliferation and metastasis.

    Evidence ChIP, RNA-IP, EMSA, reporter assays, and migration/invasion assays across breast and other cancer models

    PMID:25881544 PMID:27634883 PMID:28399911 PMID:28683467 PMID:29052531 PMID:29733656

    Open questions at the time
    • Several of these (ER, PR, ceRNA) are Low-confidence single-RIP studies without domain mutagenesis
    • in vivo relevance of many target loops untested
  9. 2018 High

    Demonstrated druggability of the eIF4E interface and provided in vivo confirmation of Rbm38-PTEN and Rbm38-p63 loops in tumor suppression, plus a viral splicing role.

    Evidence Structure-guided Pep8 peptide with xenografts, compound-mutant mouse models (mutant-p53 KI, TAp63+/-), Ago2 Co-IP in phosphomimetic MEFs, and B19V splicing assays

    PMID:29330147 PMID:29437973 PMID:29520104 PMID:30567739 PMID:30591552

    Open questions at the time
    • Therapeutic window of eIF4E-disrupting agents unknown
    • generality of the Ser195-Ago2 switch beyond p63 not yet broad
  10. 2020 High

    Delivered the structural basis of sequence-specific RNA recognition and expanded the splicing/transcription-coupling repertoire.

    Evidence X-ray crystallography of the RRM-ssRNA complex with mutagenesis, plus cell-based splicing screens (Cdh23) and transcription-elongation assays (SMEK2)

    PMID:31860021 PMID:32774357 PMID:33233740

    Open questions at the time
    • Structure of full-length RBM38 or its complexes with eIF4E/Ago2 not solved
    • how single RRM achieves diverse target outcomes unexplained
  11. 2021 High

    Refined the Ser195 fine-tuning of p53 in vivo and clarified RBM38's dual, opposing control of miRNA-mediated decay via direct AGO2 contacts.

    Evidence Multiple RBM38/eIF4E knock-in cell lines and Rbm38-S193D KI mice with cap-binding/senescence/lifespan data, plus reciprocal AGO2 Co-IP and Pep8 disruption on survivin

    PMID:32088727 PMID:33472892 PMID:33664057 PMID:34204113 PMID:34302858 PMID:34453780

    Open questions at the time
    • How RBM38 chooses between protective and decay-promoting miRNA modes on one transcript is unclear
    • several downstream cancer targets remain Low/Medium-confidence single-lab
  12. 2023 Medium

    Identified upstream regulators of RBM38 protein and expression (TRIM17 ubiquitination, CBX7-TARDBP axis) and a small-molecule eIF4E disruptor, linking RBM38 to drug resistance and cardiomyocyte cell-cycle exit.

    Evidence TRIM17 Co-IP/K48-ubiquitination assays, CBX7-TARDBP Co-IP/MS with conditional KO mice, and SAR-driven compound 094 binding/translation assays

    PMID:36940176 PMID:37158107 PMID:37219768 PMID:37296859

    Open questions at the time
    • RNF26 ubiquitin-ligase regulation not represented by a discovery in this timeline
    • mechanism coupling CBX7-TARDBP to RBM38 transcription incompletely defined
  13. 2025 High

    Established a dedicated developmental/physiological role in erythropoiesis and heme biosynthesis through multi-modal regulation of Ferrochelatase, and identified CDK4 as a second Ser195 kinase.

    Evidence Conditional/whole-body Rbm38 KO mice with Fech rescue transplants and heme measurements, and CDK4/6-inhibitor translation assays in TNBC

    PMID:40961234 PMID:41154395

    Open questions at the time
    • Coordination of splicing, decay, and translation of Fech by a single RBP not mechanistically integrated
    • CDK4 phosphorylation data are Medium-confidence single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single RRM with one defined RNA motif selects between stabilizing, destabilizing, splicing-activating, translation-repressing, and miRNA-gating outcomes on different targets remains the central unresolved question.
  • No structural model of RBM38 in its eIF4E/eIF4G/Ago2 complexes
  • no global rule predicting target outcome from binding-site context
  • interplay of competing trans-acting partners (HuR, Ago2, eIF4E/4G) on a shared transcript not quantitatively defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0045182 translation regulator activity 4 GO:0098772 molecular function regulator activity 4 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 2
Partners
AGO2EIF4EEIF4GELAVL1GSK3BPPM1DRBM24TRIM17
Complex memberships
RBM38-Ago2 miRNA complexeIF4F (eIF4E/eIF4G on p53 mRNA cap)

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 RNPC1a (RBM38 isoform) directly binds to the 3' UTR of p21 mRNA and stabilizes it, maintaining basal and stress-induced p21 transcript levels; RNPC1a but not RNPC1b induces G1 cell cycle arrest and stabilizes p21 transcript, despite both isoforms being expressed in nucleus and cytoplasm and both binding p21 3' UTR. RNA binding assays, knockdown/overexpression with mRNA stability assays, cell cycle analysis Genes & development High 17050675
2010 RNPC1 (RBM38) and HuR physically interact via the RRM domain of RNPC1 and RRM3 of HuR; RNPC1 and HuR preferentially bind upstream and downstream AU-rich elements (AREs) in p21 3'-UTR respectively; RNPC1 enhances HuR's RNA-binding activity to p21 transcript in vitro and in vivo, and RNPC1's ability to stabilize p21 mRNA is dependent on HuR. Co-immunoprecipitation, RNA immunoprecipitation, in vitro RNA binding assays, domain-mapping experiments Nucleic acids research High 20064878
2010 RNPC1 (RBM38) binds AU-/U-rich elements in p63 3' UTR via its RRM domain and destabilizes p63 transcript, reducing p63 expression; RNPC1 RRM domain is required for binding and regulating p63 mRNA stability; RNPC1 promotes keratinocyte differentiation by repressing p63 expression. RNA immunoprecipitation, in vitro RNA binding (EMSA), overexpression/knockdown with mRNA stability assays, RRM mutant analysis Proceedings of the National Academy of Sciences High 20457941
2011 RNPC1 (RBM38) represses p53 mRNA translation by preventing eIF4E from binding to p53 mRNA; RNPC1 uses its C-terminal domain to physically interact with eIF4E and its N-terminal domain to bind p53 mRNA 5' and 3' UTRs; loss of RNPC1 in MEFs increases p53 protein, leading to enhanced premature senescence in a p53-dependent manner. Overexpression/knockdown translation assays, domain-mapping Co-IP with eIF4E, RNA-binding assays with p53 5'/3' UTR, polysome profiling, MEF senescence assays Genes & development High 21764855
2011 RBM38 selectively blocks miRNA access to target mRNAs by interacting with uridine-rich regions near miRNA target sequences; RBM38 is induced by p53 and its ability to modulate miRNA-mediated repression is required for proper p53 function; RBM38 shows lower propensity to block p53-controlled miR-34a action on SIRT1. Genetic screen for RBPs controlling miRNA activity, luciferase reporter assays, RNA binding assays, RBM38 overexpression/knockdown Nature communications High 22027593
2012 RNPC1 (RBM38) destabilizes MDM2 transcript via binding to multiple AU-/U-rich elements in MDM2 3' UTR, reducing MDM2 expression independent of p53; RNA-binding activity of RNPC1 (RRM domain) is required for binding MDM2 transcript and inhibiting MDM2 expression. Overexpression/knockdown/knockout mRNA stability assays, RNA immunoprecipitation, EMSA, reporter assays with MDM2 3' UTR, RRM mutant analysis Oncogene High 22710720
2012 RNPC1 (RBM38) post-transcriptionally stabilizes HuR mRNA via binding to its 3' UTR; RNA-binding-deficient RNPC1 mutant fails to stabilize HuR transcript; HuR, by repressing c-Myc expression, mediates RNPC1-induced growth suppression. Overexpression/knockdown/knockout mRNA stability assays, RNA immunoprecipitation, RNA-binding mutant analysis The Journal of biological chemistry High 22371495
2012 p73 mRNA stability is regulated by RNPC1 (RBM38) via a CU-rich element in the p73 3' UTR; loss of RNPC1 in p53-null MEFs reduces p73 expression along with p21 and p130, decreasing senescent cell number; combined knockdown of TAp73 and p21 completely abolishes RNPC1-mediated growth suppression and senescence. Overexpression/knockdown mRNA stability assays, RNA immunoprecipitation, EMSA, siRNA epistasis in MEFs Molecular and cellular biology High 22508983
2012 RBM38 is a direct transcriptional target of E2F1; endogenous E2F1 binds the RBM38 promoter; RBM38 and E2F1 constitute a negative feedback loop limiting E2F1-induced cell-cycle progression. ChIP demonstrating E2F1 binding to RBM38 promoter, siRNA knockdown of E2F1, cell-cycle analysis with RBM38 inhibition Molecular cancer research Medium 22798430
2013 RNPC1 (RBM38) binds to an AU-rich element in MIC-1 3' UTR and stabilizes MIC-1 mRNA, increasing MIC-1 expression; knockdown of MIC-1 decreases RNPC1-induced cell growth suppression. Overexpression/knockdown/knockout mRNA stability assays, RNA immunoprecipitation, siRNA epistasis The Journal of biological chemistry Medium 23836903
2013 RBM38 regulates alternative splicing during late erythroid differentiation, including activation of Protein 4.1R (EPB41) exon 16 splicing; RBM38 directly activates splicing when recruited to a downstream intron (tethering assay); SELEX-Seq identified a GU-rich RBM38 binding motif. Exon junction splicing microarray, minigene splicing assays, SELEX-Seq for binding motif, tethering assay PloS one High 24250749
2013 GSK3 phosphorylates RNPC1 (RBM38) at Ser195; phosphorylation at Ser195 (mimicked by S195D mutant) abolishes RNPC1's interaction with eIF4E on p53 mRNA and instead promotes interaction with eIF4G, facilitating assembly of the eIF4F complex on p53 mRNA and thereby promoting p53 mRNA translation; PI3K-Akt pathway inhibition activates GSK3, increases RNPC1 phosphorylation, and increases p53 expression in an RNPC1-dependent manner. In vitro kinase assay, phosphomimetic/deletion mutant analysis, Co-IP with eIF4E and eIF4G, polysome/cap-binding assays, PI3K inhibitor treatment Genes & development High 24142875
2014 Rbm38-null mice exhibit accelerated aging, hematopoietic defects, and spontaneous tumors; Rbm38 deficiency enhances IR-induced p53 accumulation and sensitizes mice to IR-induced lethality in a p53-dependent manner; Rbm38 deficiency markedly decreases tumor penetrance in p53 heterozygous mice via enhanced p53 expression; providing in vivo genetic evidence for the p53-Rbm38 autoregulatory loop. Knockout mouse model, ionizing radiation challenge, epistasis with p53-heterozygous mice, tumor monitoring Proceedings of the National Academy of Sciences High 25512531
2015 PPM1D phosphatase directly interacts with RBM38 and dephosphorylates it at Ser195; dephosphorylated RBM38 represses p53 mRNA translation; RBM38 in turn promotes PPM1D mRNA translation by binding to PPM1D 3' UTR; creating a PPM1D-RBM38-p53 regulatory axis. Co-IP, in vitro dephosphorylation assay, RNA immunoprecipitation, reporter assays with PPM1D 3' UTR, translation/growth suppression assays Oncogene High 25823026
2015 RBM38 (RNPC1) regulates HIF1α expression via mRNA translation under hypoxia by directly binding HIF1α 5' and 3' UTRs and preventing eIF4E binding to HIF1α mRNA; knockdown of RBM38 increases de novo HIF1α protein synthesis rate. Overexpression/knockdown, de novo protein synthesis assays, RNA immunoprecipitation, cap-binding assay with eIF4E, reporter assays with HIF1α UTRs Oncotarget Medium 25622105
2017 RBM38 stabilizes PTEN mRNA by binding to multiple AU/U-rich elements in PTEN 3' UTR; PTEN inhibition partially reverses RBM38-mediated growth suppression in breast cancer cells. RNA immunoprecipitation, EMSA, dual-luciferase reporter assay, overexpression/knockdown mRNA stability assays, PTEN inhibitor/siRNA epistasis Journal of experimental & clinical cancer research Medium 29052531
2017 TGF-β induces Snail, which directly represses RBM38 transcription via E-box elements in the RBM38 promoter; RBM38 in turn stabilizes ZO-1 mRNA by binding AU/U-rich elements in ZO-1 3' UTR, and RBM38 overexpression reverses ZO-1 knockdown-mediated cell migration and invasion. ChIP assay (Snail on RBM38 promoter), luciferase reporter assay, RNA immunoprecipitation, EMSA, Transwell migration/invasion assays British journal of cancer Medium 28683467
2017 RBM38 destabilizes c-Myc mRNA by directly targeting AU-rich elements in c-Myc 3' UTR; c-Myc transcription factor suppresses RBM38 gene expression by binding E-box motifs in the RBM38 promoter, forming a mutually antagonistic RBM38–c-Myc feedback loop. ChIP assay (c-Myc on RBM38 promoter), RNA immunoprecipitation, dual-luciferase reporter assay, overexpression/knockdown with mRNA stability Journal of experimental & clinical cancer research Medium 28399911
2017 RNPC1 (RBM38) stabilizes ESR1 (ERα) mRNA by binding to AREs in ERα 3' UTR, increasing ERα expression; reciprocally, ERα overexpression decreases RNPC1 transcript and protein levels, forming a feedback loop. RNA immunoprecipitation, overexpression/knockdown mRNA stability assays Oncotarget Low 25881544
2017 RNPC1 (RBM38) stabilizes progesterone receptor (PR) mRNA by binding AU-rich elements in PR 3' UTR; RBM38 overexpression increases PR mRNA and protein and enhances progesterone-dependent proliferation in vitro and in vivo. RNA immunoprecipitation, mRNA stability assays, overexpression/knockdown, in vivo xenograft Oncotarget Low 27634883
2017 RBM38 (RNPC1) stabilizes mRNAs of STARD13, CDH5, HOXD10, and HOXD1 in breast cancer cells, promoting a ceRNA network that inhibits cancer cell metastasis. Overexpression/knockdown with mRNA stability assays, functional invasion assays Molecular pharmaceutics Low 29733656
2018 RBM38 destabilizes MDM2 mRNA through binding AU/U-rich elements in MDM2 3' UTR in HCC, restoring wild-type p53 expression and suppressing HCC cell proliferation, migration, invasion, and tumor growth in vivo. Luciferase reporter assay with MDM2 3' UTR, overexpression/knockdown, functional assays in vitro and in vivo xenograft Journal of experimental & clinical cancer research Medium 30176896
2018 An 8-amino acid peptide (Pep8) derived from the eIF4E-binding interface of RBM38 disrupts the RBM38-eIF4E complex; molecular simulations identified Ser-6 in Pep8 forms a hydrogen bond with Asp-202 in eIF4E; Pep8 relieves RBM38-mediated repression of p53 translation and suppresses tumor growth in RBM38- and p53-dependent manners. Molecular simulation, peptide competition assays, p53 translation assays, colony/tumor sphere formation, xenograft assay Cancer research High 30591552
2018 Rbm38 is required for Pten mRNA stabilization through an AU-rich element in Pten 3' UTR; genetic ablation of Rbm38 in mutant p53 knock-in mice decreases PTEN expression, enhances mutant p53 expression, and promotes T-cell lymphomagenesis. Rbm38 knockout in mutant p53 knock-in mice, mRNA stability assays, 3' UTR binding assays, tumor monitoring Cancer research High 29330147
2018 The Rbm38-p63 negative feedback loop operates in vivo: Rbm38 deficiency reduces tumor penetrance in TAp63+/- mice, extends lifespan of tumor-free TAp63+/- mice, reduces senescence markers and inflammatory cytokines (IL17D, Tnfsf15), while Rbm38-/-;TAp63+/- MEFs are resistant to cellular senescence. Compound knockout/heterozygous mouse model, lifespan monitoring, MEF senescence assays, cytokine expression analysis Oncogene High 29520104
2018 Ser-195 phosphorylation of Rbm38 by GSK3β increases p63α expression by disrupting the association of Rbm38 with the Ago2-miR203 complex; unphosphorylated WT Rbm38 associates with Ago2 and facilitates miR203-mediated p63 mRNA degradation; S195D phosphomimetic Rbm38 shows reduced Ago2 association and fails to promote p63 mRNA degradation. Phosphomimetic/phospho-null mutant knock-in MEFs, Co-IP of Rbm38 with Ago2, miR203-dependent mRNA degradation assays, GSK3β activation experiments The Journal of biological chemistry High 30567739
2018 RBM38 promotes B19V pre-mRNA splicing at the D2 donor site by binding the intronic splicing enhancer 2 (ISE2) element containing the consensus 5'-UGUGUG-3' motif; this promotes 11-kDa viral protein expression that in turn facilitates viral DNA replication and virion release. In vitro RNA binding assay confirming RBM38-ISE2 interaction, siRNA knockdown of RBM38 in erythroid cells with measurement of spliced mRNA and viral replication Journal of virology Medium 29437973
2019 Rbm38 silencing improves migratory capacity and proliferation of endothelial cells; local silencing of Rbm38 in vivo improved re-endothelialization of denuded carotid arteries; miR-98 and let-7f regulate Rbm38 (identified by luciferase reporter assay) and their overexpression mimics Rbm38 silencing effects. siRNA knockdown in HUVECs, in vivo carotid artery injury model with local Rbm38 silencing, luciferase reporter assays for miRNA regulation of Rbm38 Cardiovascular research Medium 30843048
2020 Crystal structure of the RRM domain of human RBM38 in complex with single-stranded RNA revealed that RBM38 recognizes G(U/C/A)GUG sequence in a sequence- and structure-specific manner; two phenylalanine residues stack with RNA bases and are crucial for binding; hydrogen bonds between RNA bases and RBM38 main-chain/side-chain atoms determine sequence specificity. X-ray crystallography of RRM domain–RNA complex, mutagenesis of key residues, RNA binding assays The Biochemical journal High 31860021
2020 Alternative splicing of Cdh23 exon 68 is positively regulated by RBM38 (and RBM24) and negatively regulated by PTBP1; RBM38 identified in a cell-based screen as an enhancer of Cdh23 exon 68 inclusion. Cell-based splicing screen, minigene splicing assays, siRNA knockdown of splicing factors Neural plasticity Medium 32774357
2020 Rbm38 reduces the transcription elongation defect of the SMEK2 gene caused by splicing deficiency; this requires the N- and C-terminal regions as well as the RNA recognition motif of Rbm38. Transcription elongation assays under splicing-deficient conditions, domain deletion analysis of Rbm38 International journal of molecular sciences Medium 33233740
2021 RBM38 acts as a dual regulator of survivin mRNA: it suppresses let-7b from binding and degrading survivin mRNA (increasing survivin), while also facilitating Ago2-miR-203a-mediated survivin mRNA degradation (decreasing survivin); Ser-195 in RBM38 interacts with Glu-73/-76 in AGO2, and Pep8 blocks the RBM38-AGO2 interaction, inhibiting miR-203a-mediated degradation. RNA immunoprecipitation, Co-IP of RBM38 with AGO2, miRNA competition assays, Pep8 peptide disruption, tumor spheroid viability assays Cancer research High 33472892
2021 Fine-tuning of p53 expression by RBM38-eIF4E interaction: KI of RBM38-S195D or -Y192C enhances eIF4E binding to p53 mRNA and increases p53; KI of RBM38-S195K/R/L weakens eIF4E binding and decreases p53; KI of eIF4E-D202K reduces RBM38 interaction and enhances p53; Rbm38-S193D KI mice show enhanced p53-dependent cellular senescence, shortened lifespan, and spontaneous tumors. Multiple knock-in cell lines (RBM38 and eIF4E point mutants), cap-binding assays, Rbm38-S193D KI mouse model, senescence assays, lifespan monitoring Genes & development High 33664057
2021 RNPC1 (RBM38) stabilizes MST1/2 mRNA by directly binding to it, activating the Hippo pathway; inhibition of MST1/2 rescues RNPC1-mediated attenuation of endometrial cancer sphere stemness. RNA immunoprecipitation, overexpression with stemness assays, MST1/2 inhibitor epistasis Medical science monitor Low 32088727
2021 RBM38 stabilizes AURKB (aurora kinase B) mRNA by directly binding to the AURKB 3' UTR; RNPC1 overexpression increases AURKB mRNA and protein, promotes proliferation, migration and invasion, and causes mitotic defects and chromosomal instability in gastric cancer. RNA immunoprecipitation, EMSA, dual-luciferase reporter assay, mRNA stability assay, overexpression/knockdown, in vivo xenograft Experimental cell research Medium 34302858
2021 RBM38 competes with miR-92a-3p for binding to PTEN 3' UTR, stabilizing PTEN transcript and inhibiting colorectal cancer progression; PTEN overexpression attenuates the effects of RBM38 depletion on CRC. RNA immunoprecipitation, luciferase reporter assay, competition binding assay, overexpression/knockdown, in vivo xenograft Environmental toxicology Medium 34453780
2021 SPRR2A/2D expression is regulated by an RBM38-p73 axis; RBM38 knockout reduces SPRR2A/2D expression; compound Rbm38/Trp73 double-null mice exhibit weak SPRR2A/2D expression in multiple tissues and susceptibility to systemic chronic inflammation, leading to shortened lifespan. Compound knockout mouse model, gene expression analysis, lifespan and tumor monitoring Cancers Medium 34204113
2022 RBM38 directly binds to the lower bulge of the HBV epsilon (ε) stem loop via RNA recognition submotifs (RNPs) and interacts with HBV Pol in an RNA-independent manner; RBM38 forms heterogeneous oligomers with RBM24 to mediate Pol-ε binding; RBM38 also binds HBV core via its C-terminal region (ARD domain), facilitating Pol-ε–core combination and triggering pgRNA packaging for reverse transcription. Co-immunoprecipitation (RBM38 with ε, Pol, RBM24, HBV core), RNA binding assays, domain mapping (RNPs for RNA binding, C-terminal ARD for core interaction), pgRNA packaging assays Antiviral research Medium 35041910
2023 TRIM17 interacts with RBM38 and promotes K48-linked ubiquitination and proteasomal degradation of RBM38; TRIM17-mediated cisplatin resistance in NSCLC is markedly reversed by RBM38 restoration; RBM38 enhances cisplatin-induced ROS production. Co-IP of TRIM17 with RBM38, ubiquitination assay (K48-linked), overexpression/knockdown, in vitro and in vivo cisplatin resistance assays Cellular oncology Medium 37219768
2023 CBX7 interacts with TARDBP (TDP-43) and positively regulates RBM38 expression in a TARDBP-dependent manner; overexpression of RBM38 inhibits proliferation of CBX7-depleted neonatal cardiomyocytes, placing RBM38 downstream of the CBX7-TARDBP axis in controlling cardiomyocyte cell cycle exit. Co-immunoprecipitation (CBX7-TARDBP), mass spectrometry, adenoviral overexpression of CBX7/RBM38, conditional Cbx7 knockout mice, cardiomyocyte proliferation marker immunostaining Circulation Medium 37158107
2023 Small molecule compound 094 interacts with eIF4E via the same pocket as Pep8, dissociates RBM38 from eIF4E, and enhances TP53 mRNA translation in RBM38- and eIF4E-dependent manners; fluorobenzene and ethyl benzamide moieties are necessary for compound 094-eIF4E interaction; compound 094 suppresses tumor spheroid growth in RBM38- and TP53-dependent manners. Structure-activity relationship studies, eIF4E binding assays, p53 translation assays (polysome profiling/reporter), tumor spheroid assays, combination assays with doxorubicin/4EGI-1 Molecular cancer therapeutics High 36940176
2023 RBM38 binds and stabilizes lncRNA GAS5 in sorafenib-resistant HCC cells; RBM38 reverses sorafenib resistance in HCC both in vitro and in vivo in a GAS5-dependent manner. RNA immunoprecipitation, overexpression/knockdown, drug resistance assays, in vivo xenograft, GAS5 knockdown epistasis Cancers Low 37296859
2025 CDK4 phosphorylates RBM38 at Ser195; CDK4/6 inhibitors suppress mutant p53 mRNA translation through RBM38 by reducing Ser195 phosphorylation, which shifts RBM38 interaction from eIF4G (translation promotion) to eIF4E (translation repression) on p53 mRNA. CDK4/6 inhibitor treatment with RBM38 phosphorylation analysis, translation assays with p53 mRNA, RBM38 overexpression/knockdown, cell survival assays in RB-proficient and -deficient TNBC cells Cancers Medium 41154395
2025 Rbm38 regulates terminal erythropoiesis and heme biosynthesis by modulating alternative splicing, mRNA decay, and translation of Ferrochelatase (Fech); Rbm38-deficient mice develop microcytic hypochromic anemia, erythropoietic protoporphyria-like disease with PPIX accumulation; enforced Fech expression largely restores erythroid differentiation in Rbm38-null transplants. Conditional and whole-body knockout mouse models, transcriptome/splicing analysis, Fech rescue experiments (reconstitution transplant), erythroid differentiation assays, heme biosynthesis measurements Blood High 40961234
2026 In zebrafish, Rbm38 destabilizes pdx1 mRNA by binding to its 3' UTR and regulates alternative splicing of isl1a, smad2, and nkx2.2a; loss of Rbm38 leads to abnormal pancreatic enlargement. Zebrafish rbm38 loss-of-function, mRNA stability assays for pdx1 3' UTR binding, alternative splicing analysis for isl1a/smad2/nkx2.2a, pancreatic morphology assessment Journal of molecular cell biology Medium 40796306

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. Genes & development 125 17050675
2011 Translational repression of p53 by RNPC1, a p53 target overexpressed in lymphomas. Genes & development 118 21764855
2010 RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability. Nucleic acids research 101 20064878
2011 Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity. Nature communications 85 22027593
2010 RNPC1, an RNA-binding protein and a target of the p53 family, regulates p63 expression through mRNA stability. Proceedings of the National Academy of Sciences of the United States of America 76 20457941
2014 Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors. Proceedings of the National Academy of Sciences of the United States of America 64 25512531
2009 RNA-binding proteins Rbm38 and Rbm24 regulate myogenic differentiation via p21-dependent and -independent regulatory pathways. Genes to cells : devoted to molecular & cellular mechanisms 60 19817877
2013 Glycogen synthase kinase 3 promotes p53 mRNA translation via phosphorylation of RNPC1. Genes & development 56 24142875
2012 p73 expression is regulated by RNPC1, a target of the p53 family, via mRNA stability. Molecular and cellular biology 51 22508983
2018 RBM38 plays a tumor-suppressor role via stabilizing the p53-mdm2 loop function in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 48 30176896
2017 PTEN expression is upregulated by a RNA-binding protein RBM38 via enhancing its mRNA stability in breast cancer. Journal of experimental & clinical cancer research : CR 48 29052531
2013 The RNA binding protein RBM38 (RNPC1) regulates splicing during late erythroid differentiation. PloS one 44 24250749
2017 RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer. British journal of cancer 43 28683467
2012 MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability. Oncogene 43 22710720
2014 RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer. BMC cancer 41 24884756
2018 Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression. Cancer research 39 30591552
2018 RNA Binding Protein RNPC1 Inhibits Breast Cancer Cell Metastasis via Activating STARD13-Correlated ceRNA Network. Molecular pharmaceutics 36 29733656
2012 The RNA-binding protein RNPC1 stabilizes the mRNA encoding the RNA-binding protein HuR and cooperates with HuR to suppress cell proliferation. The Journal of biological chemistry 35 22371495
2017 The role of c-Myc-RBM38 loop in the growth suppression in breast cancer. Journal of experimental & clinical cancer research : CR 34 28399911
2012 RBM38 is a direct transcriptional target of E2F1 that limits E2F1-induced proliferation. Molecular cancer research : MCR 30 22798430
2015 The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation. Leukemia research 29 26740055
2018 Genetic Ablation of Rbm38 Promotes Lymphomagenesis in the Context of Mutant p53 by Downregulating PTEN. Cancer research 28 29330147
2013 RNPC1, an RNA-binding protein and a p53 target, regulates macrophage inhibitory cytokine-1 (MIC-1) expression through mRNA stability. The Journal of biological chemistry 28 23836903
2012 Radiation sensitivity of esophageal adenocarcinoma: the contribution of the RNA-binding protein RNPC1 and p21-mediated cell cycle arrest to radioresistance. Radiation research 27 22214381
2015 PPM1D phosphatase, a target of p53 and RBM38 RNA-binding protein, inhibits p53 mRNA translation via dephosphorylation of RBM38. Oncogene 25 25823026
2021 miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling. Aging cell 24 34751998
2015 Hypoxia-inducible factor 1 alpha is regulated by RBM38, a RNA-binding protein and a p53 family target, via mRNA translation. Oncotarget 23 25622105
2015 Estrogen receptor (ER) was regulated by RNPC1 stabilizing mRNA in ER positive breast cancer. Oncotarget 22 25881544
2020 RBM38 in cancer: role and mechanism. Cellular and molecular life sciences : CMLS 21 32642788
2017 The expression of RNA-binding protein RBM38 decreased in renal cell carcinoma and represses renal cancer cell proliferation, migration, and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 28459215
2018 RNA Binding Protein RBM38 Regulates Expression of the 11-Kilodalton Protein of Parvovirus B19, Which Facilitates Viral DNA Replication. Journal of virology 20 29437973
2021 RNA-binding protein RBM38 inhibits colorectal cancer progression by partly and competitively binding to PTEN 3'UTR with miR-92a-3p. Environmental toxicology 19 34453780
2018 The Rbm38-p63 feedback loop is critical for tumor suppression and longevity. Oncogene 19 29520104
2023 Polycomb Group Protein CBX7 Represses Cardiomyocyte Proliferation Through Modulation of the TARDBP/RBM38 Axis. Circulation 18 37158107
2017 RNPC1 enhances progesterone receptor functions by regulating its mRNA stability in breast cancer. Oncotarget 17 27634883
2017 RNPC1 inhibits non-small cell lung cancer progression via regulating miR-181a/CASC2 axis. Biotechnology letters 17 29288351
2023 TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer. Cellular oncology (Dordrecht, Netherlands) 16 37219768
2020 Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1. Neural plasticity 15 32774357
2017 The RNA-binding protein Rbm38 is dispensable during pressure overload-induced cardiac remodeling in mice. PloS one 14 28850611
2015 Integrative genomic analyses of the RNA-binding protein, RNPC1, and its potential role in cancer prediction. International journal of molecular medicine 14 26046131
2018 Serine 195 phosphorylation in the RNA-binding protein Rbm38 increases p63 expression by modulating Rbm38's interaction with the Ago2-miR203 complex. The Journal of biological chemistry 13 30567739
2022 LncRNA CALML3-AS1 suppresses papillary thyroid cancer progression via sponging miR-20a-5p/RBM38 axis. BMC cancer 12 35351042
2017 TAp63γ and ΔNp63γ are regulated by RBM38 via mRNA stability and have an opposing function in growth suppression. Oncotarget 12 29108232
2020 Structural basis for mRNA recognition by human RBM38. The Biochemical journal 11 31860021
2019 Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury. Cardiovascular research 10 30843048
2022 RNA-Binding motif protein 38 (RBM38) mediates HBV pgRNA packaging into the nucleocapsid. Antiviral research 9 35041910
2021 Fine-tuning p53 activity by modulating the interaction between eukaryotic translation initiation factor eIF4E and RNA-binding protein RBM38. Genes & development 8 33664057
2021 RBM38 is negatively regulated by miR-320b and enhances Adriamycin resistance in breast cancer cells. Oncology letters 8 34868364
2020 RNA Binding Protein RNPC1 Suppresses the Stemness of Human Endometrial Cancer Cells via Stabilizing MST1/2 mRNA. Medical science monitor : international medical journal of experimental and clinical research 8 32088727
2023 Identification of a First-in-Class Small-Molecule Inhibitor of the EIF4E-RBM38 Complex That Enhances Wild-type TP53 Protein Translation for Tumor Growth Suppression. Molecular cancer therapeutics 7 36940176
2023 RBM38 Reverses Sorafenib Resistance in Hepatocellular Carcinoma Cells by Combining and Promoting lncRNA-GAS5. Cancers 7 37296859
2019 RBM38 induces SIRT1 expression during hypoxia in non-small cell lung cancer cells by suppressing MIR34A expression. Biotechnology letters 7 31760527
2017 RNA-binding protein RBM38 acts as a tumor suppressor in gastric cancer. International journal of clinical and experimental pathology 7 31966462
2021 Survivin Expression Is Differentially Regulated by a Selective Cross-talk between RBM38 and miRNAs let-7b or miR-203a. Cancer research 6 33472892
2020 Roles of ZEB2 and RBM38 in liver cancer stem cell proliferation. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 6 32862581
2021 RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA. Experimental cell research 5 34302858
2021 Small Proline-Rich Protein 2A and 2D Are Regulated by the RBM38-p73 Axis and Associated with p73-Dependent Suppression of Chronic Inflammation. Cancers 4 34204113
2023 RNF26 Promotes Pancreatic Cancer Proliferation by Enhancing RBM38 Degradation. Pancreas 3 37099788
2022 Optimization of eIF4E-Binding Peptide Pep8 to Disrupt the RBM38-eIF4E Complex for Induction of p53 and Tumor Suppression. Frontiers in oncology 3 35574389
2020 Rbm38 Reduces the Transcription Elongation Defect of the SMEK2 Gene Caused by Splicing Deficiency. International journal of molecular sciences 3 33233740
2025 Rbm38 deficiency impairs erythroid heme biosynthesis and induces porphyria via reduced ferrochelatase expression. Blood 2 40961234
2016 [RNPC1 induces sensitivity of HER-2-positive breast cancer BT474 cells to trastuzumab through upregulation of HER2]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 2 26988821
2026 RNA-binding protein Rbm38 as a multifaceted post-transcriptional regulator in zebrafish pancreatic development. Journal of molecular cell biology 0 40796306
2025 EIF4A3-Mediated downregulation of circPTEN promotes hepatocellular carcinoma progression through the miR-1289/RBM38 Axis. Journal of molecular histology 0 40527976
2025 CDK4/6 Inhibitors Suppress RB-Null Triple-Negative Breast Cancer by Inhibiting Mutant P53 Expression via RBM38 RNA-Binding Protein. Cancers 0 41154395
2021 [RBM38 Mediates the Proliferation of Acute Myeloid Leukemia Cells HL-60 by Regulating FZD1 mRNA Stability]. Zhongguo shi yan xue ye xue za zhi 0 34893109

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