Affinage

RBM3

RNA-binding protein 3 · UniProt P98179

Length
157 aa
Mass
17.2 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM3 is a cold-shock RNA-binding protein that functions as a broad translational and post-transcriptional regulator, coupling environmental stress sensing to mRNA fate, miRNA biogenesis, and cell survival across neuronal, immune, and proliferative contexts. Its N-terminal RRM domain (βαββαβ topology) binds RNA via a beta-sheet/loop interface and forms temperature-dependent oligomers; RBM3 associates with 60S ribosomal subunits in an RNA-independent manner and enhances global protein synthesis, polysome assembly, and IRES-mediated cap-independent translation of its own mRNA, while also regulating local synaptic translation in neurons (PMID:15684048, PMID:11470798, PMID:34837346, PMID:33310754). RBM3 stabilizes specific target mRNAs — including Yap1, GAS6, SOX11, ARPC2, MMP9, and RTN3 — through 3′UTR binding, promotes pre-miRNA processing at the Dicer step, and regulates alternative splicing of CD44 (PMID:30037926, PMID:22145045, PMID:23667174, PMID:28238655). Cold-induced RBM3 expression is controlled transcriptionally by NF-κB p65 and TrkB/PLCγ1/pCREB signaling, and post-transcriptionally by temperature-sensitive inclusion of a poison exon repressed by HNRNPH1; RBM3 is required for hypothermia-induced neuroprotection, mediating synapse regeneration through the RTN3 axis, suppressing PERK–eIF2α–CHOP ER stress via NF90, exerting negative feedback on ERK signaling through DUSP6, and intrinsically restraining innate lymphoid cell activation (PMID:37248947, PMID:25607368, PMID:26472337, PMID:33563652, PMID:35908044).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 Medium

    Identifying RBM3 as a cold- and translational-stress-inducible gene established the founding observation that mammalian cells mount a specific transcriptional response to mild hypothermia, paralleling bacterial cold-shock proteins.

    Evidence RT-PCR and Northern blot across multiple human cell lines at 32°C and with protein synthesis inhibitors

    PMID:9245737

    Open questions at the time
    • Mechanism of cold sensing upstream of transcription unknown
    • Protein-level induction not confirmed
  2. 2001 High

    Discovery that the RBM3 5′ leader contains a cold-enhanced IRES resolved how RBM3 protein accumulates under hypothermia despite global cap-dependent translation suppression, revealing a feed-forward autoregulatory loop.

    Evidence Dicistronic reporter assays in cells and cell-free lysates at 33°C vs 37°C

    PMID:11470798

    Open questions at the time
    • Trans-acting factors required for IRES activity not identified
    • In vivo relevance of IRES not demonstrated
  3. 2003 High

    Dissecting the modular architecture of the RBM3 IRES — identifying a 22-nt module that directly binds 40S subunits — provided the first cis-element map for a mammalian cold-responsive IRES.

    Evidence Deletion/mutational analysis with 40S ribosomal subunit binding assays in vitro

    PMID:12824175

    Open questions at the time
    • Structure of IRES-40S complex not resolved
    • Contribution of each module in vivo unknown
  4. 2005 High

    Demonstrating that RBM3 overexpression enhances global protein synthesis 3-fold and that RBM3 associates with 60S ribosomal subunits in an RNA-independent manner established RBM3 as a direct translational stimulator rather than merely a stress-response marker.

    Evidence Radioactive amino acid incorporation; polysome profiling and sucrose gradient fractionation in N2a cells

    PMID:15684048

    Open questions at the time
    • Mechanism by which 60S association promotes translation initiation unclear
    • Whether endogenous RBM3 levels are sufficient for this effect untested
  5. 2007 High

    Localizing RBM3 to neuronal dendrites and showing isoform-dependent dendritic targeting extended the translational stimulation model to local synaptic translation, linking RBM3 to neuronal plasticity.

    Evidence Immunofluorescence in dissociated neurons; sucrose gradient co-fractionation with translation machinery; alternatively spliced isoform overexpression

    PMID:17403028

    Open questions at the time
    • Specific dendritic mRNA targets not identified
    • Functional consequence for synaptic plasticity not tested
  6. 2008 High

    Showing that RBM3 knockdown causes mitotic catastrophe with G2 checkpoint activation, while overexpression promotes proliferation and stabilizes COX-2/VEGF/IL-8 mRNAs, revealed RBM3's dual role in cell cycle progression and selective mRNA stabilization relevant to oncogenesis.

    Evidence siRNA knockdown in HCT116; overexpression in NIH3T3/SW480; soft agar and xenograft assays; mRNA stability measurements

    PMID:18427544

    Open questions at the time
    • Direct RNA binding to COX-2/VEGF/IL-8 not demonstrated with purified protein
    • Mechanism of mitotic catastrophe induction not resolved
  7. 2011 High

    Three concurrent advances — demonstrating RBM3's essential role in hypothermic neuroprotection, its regulation of miRNA biogenesis at the Dicer step, and G2-phase accumulation in Rbm3-null MEFs — collectively established RBM3 as a multi-level post-transcriptional regulator with in vivo physiological importance.

    Evidence siRNA/overexpression in primary neurons and organotypic slices (PARP cleavage, LDH release); miRNA arrays plus pre-miRNA binding and Dicer activity assays; Rbm3 KO MEFs with flow cytometry

    PMID:21527344 PMID:21684257 PMID:22145045

    Open questions at the time
    • Specific miRNAs mediating neuroprotection not identified
    • Relationship between miRNA regulation and cell cycle control unexplored
    • Direct structural basis for pre-miRNA recognition unknown
  8. 2013 High

    Identifying RBM3 as a regulator of CD44 alternative splicing (shifting v8-v10 to standard isoform) linked the protein's RNA-binding activity to splicing regulation with consequences for cancer stemness properties.

    Evidence RBM3 overexpression/silencing in prostate cancer cells; RT-PCR for CD44 isoforms; soft agar and in vivo tumorigenicity

    PMID:23667174

    Open questions at the time
    • Whether RBM3 directly binds CD44 pre-mRNA or acts indirectly not resolved
    • Generality of splicing regulation beyond CD44 unknown
  9. 2015 High

    Two key findings — that RBM3 mediates synapse regeneration after cooling in neurodegenerative mouse models and that it suppresses ER stress via NF90-dependent inhibition of the PERK-eIF2α-CHOP pathway — provided the first in vivo mechanism linking cold-induced RBM3 to structural neuroprotection and proteostasis.

    Evidence Prion and 5XFAD mouse models with lentiviral RBM3 overexpression/knockdown; behavioral and survival assays; AP-MS, Co-IP, and PLA identifying NF90; PERK phosphorylation in RBM3 KO hippocampal slices

    PMID:25607368 PMID:26472337

    Open questions at the time
    • Full set of RBM3 target mRNAs driving synapse regeneration not catalogued
    • Whether NF90 interaction is direct or RNA-bridged not fully resolved
  10. 2017 High

    Identification of RTN3 as a downstream effector of RBM3-mediated neuroprotection, and of FAK/Src signaling as an upstream transcriptional inducer of RBM3, placed RBM3 within a defined signaling cascade from cold sensing to synaptic repair.

    Evidence Ribosome profiling identifying RTN3; lentiviral RTN3 rescue in neurodegeneration model; FAK/Src inhibitors and siRNA blocking RBM3 induction

    PMID:28238655 PMID:33272569

    Open questions at the time
    • How RBM3 binding to RTN3 mRNA enhances its translation not mechanistically resolved
    • Integration of FAK/Src with NF-κB and TrkB pathways not established
  11. 2018 Medium

    Demonstrating that NF-κB p65, phosphorylated at Ser276 by hypothermia, directly binds the RBM3 promoter established a concrete transcription factor–promoter mechanism for cold-induced RBM3 expression.

    Evidence CAPE inhibition of NF-κB; promoter binding analysis; rescue by RBM3 overexpression; apoptosis assays

    PMID:29388696

    Open questions at the time
    • ChIP-seq for p65 on RBM3 promoter not performed
    • Relationship between p65 Ser276 phosphorylation and cold sensing unclear
  12. 2019 High

    A cluster of studies identified direct 3′UTR binding targets of RBM3 (Yap1, ARPC2 mRNAs) and an interacting partner (IMP2) linking RBM3 to IGF2 release in neural stem cells, expanding the catalogue of RBM3-stabilized transcripts and establishing niche-specific signaling downstream of RBM3.

    Evidence 3′UTR binding assays with KO rescue for Yap1; RNA pulldown for ARPC2; Co-IP plus ELISA for IMP2-IGF2 axis in SGZ neural stem cells after HI injury

    PMID:30037926 PMID:30720048 PMID:31484925

    Open questions at the time
    • Transcriptome-wide binding map in neurons not available at this point
    • Whether IMP2 interaction is RNA-dependent not tested
  13. 2021 High

    Discovery of the TrkB/PLCγ1/pCREB–RBM3–DUSP6 signaling axis, where RBM3 provides negative feedback on ERK via DUSP6, and that TrkB agonism can substitute for cooling to induce RBM3 and prevent neurodegeneration, defined a pharmacologically actionable pathway for RBM3 induction.

    Evidence TrkB antagonist/agonist treatment in prion-diseased mice and RBM3-null neurons; Western blot for PLCγ1, pCREB, ERK, DUSP6

    PMID:33563652

    Open questions at the time
    • Whether TrkB-RBM3 axis operates outside the nervous system untested
    • Mechanism by which RBM3 induces DUSP6 (transcriptional vs post-transcriptional) not determined
  14. 2021 High

    Structural determination of the RBM3 RRM domain by NMR, revealing its βαββαβ fold, RNA-binding interface, and temperature-dependent oligomerization, provided the first atomic-level framework for understanding how RBM3 senses temperature and engages RNA.

    Evidence Solution NMR; NMR-monitored RNA titration; molecular dynamics; SEC and cross-linking for oligomerization

    PMID:34837346

    Open questions at the time
    • Structure of full-length RBM3 including glycine-rich C-terminal domain not solved
    • Oligomer interface residues not mapped by mutagenesis
    • No structure of RBM3 bound to a physiological RNA target
  15. 2021 High

    Demonstrating that Rbm3-null innate lymphoid cells show cell-intrinsic hyperactivation and increased CysLT1R expression, with epistasis via double KO, extended RBM3 function beyond neurons into immune regulation.

    Evidence Rbm3−/− and Rbm3−/−Rag2−/− mice; bone marrow chimeras; allergen challenge; RNA-seq; Rbm3/Cyslt1r double KO

    PMID:35908044

    Open questions at the time
    • Direct RNA targets mediating ILC suppression not identified
    • Whether RBM3 regulates CysLT1R mRNA directly not tested
  16. 2023 High

    Discovery that cold-induced RBM3 expression is post-transcriptionally controlled by a poison exon whose temperature-sensitive inclusion (regulated by HNRNPH1 binding a G-rich motif) triggers NMD, and that ASO-mediated exon skipping raises RBM3 at normothermia and is neuroprotective, provided both a mechanistic explanation for temperature-dependent regulation and a therapeutic strategy.

    Evidence Genome-wide CRISPR screen in iPSC-derived neurons; HNRNPH1 KO; ASO treatment in prion-diseased mice; splicing and NMD analysis

    PMID:36946385 PMID:37248947

    Open questions at the time
    • Thermosensor mechanism for HNRNPH1 binding affinity change not structurally defined
    • Long-term safety of ASO-mediated RBM3 induction not assessed
  17. 2023 Medium

    Identification of RBM3's ability to upregulate m6A methylation on CTNNB1 mRNA in a METTL3-dependent manner, and its binding to SLC7A11 and GAS6 mRNAs, expanded the post-transcriptional repertoire to include epitranscriptomic regulation and ferroptosis modulation.

    Evidence m6A analysis with METTL3 dependence for CTNNB1; RNA pulldown/MS for SLC7A11; RIP for GAS6; xenograft and brain injury models

    PMID:36750551 PMID:37170022 PMID:38555015

    Open questions at the time
    • Whether RBM3 directly recruits METTL3 or acts indirectly not determined
    • RBM3-SLC7A11 interaction described as indirect downregulation — direct binding specificity unclear
    • Replication across independent labs needed
  18. 2024 Medium

    RIP-seq in skeletal muscle and scRNA-seq in neural stem cells refined the target mRNA landscape, identifying a preferred binding motif at the CDS-3′UTR junction and specific targets (SOX11, contractile apparatus genes) linking RBM3 to differentiation programs.

    Evidence RIP-seq with motif analysis in muscle; scRNA-seq with mRNA stability assays for SOX11 in NSCs; proteomic profiling of RBM3-overexpressing myoblasts

    PMID:36750123 PMID:38523796 PMID:38688991

    Open questions at the time
    • CLIP-based binding maps at nucleotide resolution not yet available
    • Functional validation of most RIP-seq targets not performed
    • Single-lab studies awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: how does RBM3 oligomerization relate to its RNA-binding selectivity and translational stimulation; what is the full-length structure including the glycine-rich domain; how are target mRNA specificity and the diverse downstream outcomes (translation, splicing, miRNA biogenesis, m6A) coordinated; and whether ASO-mediated poison exon skipping is broadly therapeutic beyond prion disease.
  • No CLIP-seq map of endogenous RBM3 binding at nucleotide resolution
  • No full-length structural model
  • Mechanism linking 60S association to translation enhancement unresolved
  • In vivo relevance of many target mRNAs identified in single studies not confirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 11 GO:0098772 molecular function regulator activity 4 GO:0140098 catalytic activity, acting on RNA 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005840 ribosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
HNRNPH1IGF2BP2METTL3NF90PIK3R1RPTOR

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 RBM3 transcript levels are increased in human cells in response to cold stress (32°C), and this induction is also triggered by protein synthesis inhibitors cycloheximide and puromycin, establishing it as a cold-shock and translational stress-responsive gene. RT-PCR and Northern blot in multiple human cell lines; protein synthesis inhibitor treatment Biochemical and biophysical research communications Medium 9245737
2001 The 5' leader of Rbm3 mRNA contains an internal ribosome entry site (IRES) that mediates cap-independent translation, with activity enhanced up to 5-fold at mild hypothermia (33°C) compared to 37°C, explaining how Rbm3 protein levels increase even when global cap-dependent translation is suppressed by cold. Dicistronic reporter mRNA transfection in cells and cell-free lysates; IRES activity assay at different temperatures The Journal of biological chemistry High 11470798
2003 The Rbm3 mRNA IRES is highly modular, composed of at least 9 discrete cis-acting sequences including a 22-nt IRES module, a 10-nt enhancer, and 2 inhibitory sequences; the 22-nt module binds directly to 40S ribosomal subunits to facilitate translation initiation. Deletion and mutational analysis of IRES; 40S ribosomal subunit binding assay; cytoplasmic protein binding studies The Journal of biological chemistry High 12824175
2004 RBM3 (and CIRP) transcription is induced by hypoxia independently of HIF-1 and mitochondria, as shown in HIF-1α-deficient, HIF-1β-deficient, and mitochondria-depleted cells; induction is blocked by actinomycin-D and respiratory chain inhibitors, and confirmed by nuclear run-on assays. Nuclear run-on assay; actinomycin-D treatment; HIF-1-deficient cell lines; mitochondria-depleted cells; respiratory chain inhibitors Journal of cell science High 15075239
2005 Rbm3 overexpression in mouse neuroblastoma N2a cells enhances global protein synthesis 3-fold; a fraction of Rbm3 associates with 60S ribosomal subunits in an RNA-independent manner; Rbm3 expression alters microRNA levels (reduces a complex sedimenting between gradient top and 40S subunits that contains microRNA). Protein synthesis assay (radioactive incorporation); polysome profiling; sucrose gradient fractionation; c-Myc fusion protein overexpression Proceedings of the National Academy of Sciences of the United States of America High 15684048
2007 RBM3 localizes to dendrites in neurons, co-fractionates with heavy mRNA granules and translation machinery components in sucrose gradients, and overexpression of RBM3 isoforms enhances global translation, active polysome formation, and initiation factor activation in neuronal cell lines; the isoform lacking a spliced arginine shows higher dendritic localization. Sucrose gradient fractionation; immunofluorescence in dissociated neurons; overexpression of alternatively spliced isoforms; polysome profiling Journal of neurochemistry High 17403028
2008 RBM3 overexpression in NIH3T3 and SW480 cells increases cell proliferation and anchorage-independent growth; RBM3 knockdown in HCT116 cells causes growth arrest, mitotic catastrophe with nuclear cyclin B1 accumulation and phosphorylation of Cdc25c, Chk1, Chk2; RBM3 enhances COX-2, IL-8, and VEGF mRNA stability and translation. siRNA knockdown; forced overexpression; soft agar colony assay; tumor xenograft; caspase assays; mRNA stability and translation assays Oncogene High 18427544
2011 RBM3 knockdown in fibroblasts and HEK293 cells reduces cell viability and leads to cell death without caspase-3-mediated apoptosis; RBM3 overexpression rescues cells from serum starvation-induced death and is associated with increased translation rates (measured by radiolabeled amino acid incorporation). siRNA knockdown; overexpression; cell viability assay; radiolabeled amino acid incorporation for translation measurement Pediatric research Medium 19770690
2011 RBM3 is required for hypothermia-induced neuroprotection in neurons; RBM3 overexpression reduces PARP cleavage, prevents internucleosomal DNA fragmentation, and reduces LDH release; siRNA knockdown of RBM3 significantly diminishes the neuroprotective effect of hypothermia. siRNA knockdown; vector-driven overexpression; primary neurons, PC12 cells, cortical organotypic slice cultures; PARP cleavage assay; DNA fragmentation assay; LDH release assay Neurobiology of disease High 21527344
2011 RBM3 is an essential regulator of miRNA biogenesis at the Dicer processing step: RBM3 knockdown downregulates >60% of detectable miRNAs in neuronal cells (affecting ~70 nt precursor levels without changing primary transcripts or Dicer activity); RBM3 binds directly to ~70 nt pre-miRNA intermediates and promotes their association with active Dicer complexes. miRNA array; Northern blot; PCR; RBM3 knockdown/overexpression; pre-miRNA binding assay; Dicer activity assay; subcellular fractionation for nuclear transport PloS one High 22145045
2011 RBM3-deficient (Rbm3−/−) mouse embryonic fibroblasts show markedly increased G2-phase cell accumulation compared to controls, indicating a role for RBM3 in G2-phase cell cycle control. Generation of Rbm3 knockout mice; cell cycle analysis of MEFs by flow cytometry Biochemical and biophysical research communications Medium 21684257
2013 RBM3 overexpression or culture at 32°C suppresses alternative splicing of CD44 variant v8-v10 and increases standard CD44s isoform in prostate cancer cells; RBM3 silencing increases CD44v8-v10 to CD44s ratio; elevated CD44v8-v10 interferes with MMP9-mediated cleavage of CD44s and suppresses cyclin D1 expression, linking RBM3 to stress-regulated RNA splicing and stem cell-like properties. RBM3 overexpression; siRNA silencing; RT-PCR for CD44 isoforms; soft agar colony assay; in vivo tumorigenicity Cancer research High 23667174
2015 RBM3 mediates synapse regeneration after cooling in the brain; failure to induce RBM3 in prion-infected and 5XFAD mouse models impairs synapse reassembly after cooling; RBM3 overexpression (by hypothermic boosting or lentiviral delivery) restores synapse regeneration, prevents behavioral deficits and neuronal loss, and prolongs survival; RBM3 knockdown exacerbates synapse loss. Prion and 5XFAD mouse models; lentiviral RBM3 overexpression; cooling experiments; synapse quantification; behavioral testing; survival analysis; RBM3 siRNA knockdown Nature High 25607368
2015 RBM3 inhibits the PERK-eIF2α-CHOP ER stress pathway through cooperation with NF90; RBM3 knockout exacerbates PERK-eIF2α-CHOP signaling in hippocampal slices; overexpression of RBM3 prevents PERK phosphorylation; affinity purification-mass spectrometry, Co-IP, and proximity ligation assay identify NF90 as a novel RBM3 interactor and show NF90 interacts with PERK in an RNA-dependent manner. RBM3 knockout mouse hippocampal slices; siRNA knockdown; overexpression in HEK293 cells; affinity purification-mass spectrometry; co-immunoprecipitation; proximity ligation assay; Western blot for PERK/eIF2α/CHOP phosphorylation FASEB journal High 26472337
2017 RTN3 (reticulon protein) is a downstream effector of RBM3-mediated neuroprotection: cooling induces RTN3 expression partly by RBM3 binding to RTN3 mRNA; RTN3 overexpression independently prevents synaptic loss and cognitive deficits in a neurodegeneration mouse model; RTN3 knockdown eliminates cooling-induced neuroprotection. Ribosome profiling/translatome analysis; RBM3 knockdown/overexpression; lentiviral RTN3 overexpression; mouse neurodegeneration model; siRNA knockdown of RTN3; behavioral and synaptic assays Current biology : CB High 28238655
2018 NF-κB p65, phosphorylated at Ser276 by hypothermia, binds the RBM3 promoter and activates RBM3 transcription; inhibition of NF-κB p65 nuclear translocation by CAPE decreases RBM3 mRNA/protein and increases apoptosis that is rescued by RBM3 overexpression, establishing NF-κB p65 as a transcriptional activator of RBM3. NF-κB inhibitor CAPE; RBM3 overexpression; promoter binding analysis; Western blot for p65 phosphorylation; apoptosis assays Journal of cellular biochemistry Medium 29388696
2018 RBM3 directly interacts with PI3K subunit p85 in nasopharyngeal carcinoma cells, activating the AKT/Bcl-2 signaling pathway to confer radioresistance; AKT inhibition attenuates RBM3-mediated radioresistance. Co-immunoprecipitation; RBM3 knockdown and overexpression; AKT inhibitor treatment; apoptosis and clonogenic assays American journal of translational research Medium 30662656
2019 RBM3 interacts with IGF2 mRNA-binding protein 2 (IMP2), elevates its expression, and stimulates IGF2 release in the subgranular zone (SGZ) but not subventricular zone (SVZ) neural stem/progenitor cells after hypoxic-ischemic brain injury, establishing a niche-dependent RBM3-IMP2-IGF2 signaling pathway promoting neurogenesis. Co-immunoprecipitation; RBM3 overexpression/knockdown; ELISA for IGF2; BrdU incorporation; in vivo HI brain injury model; immunofluorescence Nature communications High 31484925
2019 RBM3 binds to the 3'UTR of Yap1 mRNA (at seven identified binding sites) and stabilizes it, thereby increasing YAP1 protein expression and affecting neuronal differentiation during embryonic brain development under cold stress. RNA-binding motif analysis; 3'UTR binding assays; RBM3 knockout in vivo; mRNA stability assay; RBM3 and YAP1 overexpression rescue in KO The Journal of cell biology High 30037926
2019 RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating biogenesis of the circular RNA SCD-circRNA 2; RBM3-mediated HCC cell proliferation is SCD-circRNA 2-dependent. RBM3 overexpression/modulation; RNA-seq; functional proliferation assays; circRNA quantification EBioMedicine Medium 31235426
2019 RBM3 upregulates ARPC2 through post-transcriptional binding to ARPC2 3'UTR mRNA, promoting breast cancer cell proliferation and metastasis; knockdown of RBM3 decreases ARPC2 expression and reduces proliferation and metastasis. RBM3 knockdown; RNA pulldown/3'UTR binding; Western blot; proliferation and migration assays International journal of oncology Medium 30720048
2020 RBM3 knockdown in hippocampal neurons specifically alters local synaptic translation without affecting global cellular translation, and changes synaptic vesicle dynamics and neuronal activity patterns; RBM3 amounts change specifically at synapses over 24-hour cycles. Transcriptome analysis at different time points; siRNA knockdown; synaptic vesicle dynamics assay; local translation measurement; live imaging The Journal of neuroscience Medium 33310754
2021 Cooling induces RBM3 via activation of TrkB through PLCγ1 and pCREB signaling; RBM3 in turn exerts negative feedback on TrkB-induced ERK activation by inducing the ERK-specific phosphatase DUSP6; TrkB antagonism abrogates cooling-induced RBM3 induction and neuroprotection in prion-diseased mice; TrkB agonism induces RBM3 without cooling, preventing neurodegeneration. Pharmacological TrkB antagonism/agonism; RBM3-null neurons; prion disease mouse model; Western blot for PLCγ1, pCREB, ERK, DUSP6; synapse/neurodegeneration assays Life science alliance High 33563652
2021 NMR structure of the N-terminal 84-residue RNA recognition motif (RRM) of human RBM3 was solved; the RRM adopts a βαββαβ topology; the beta-sheet and two loops form the RNA-binding interface via hydrogen bond, pi-pi, and pi-cation interactions; RBM3 forms temperature-dependent oligomers in solution via the RRM domain, favored by decreasing temperature. Solution NMR structure determination; NMR-monitored titration with RNA; molecular dynamics simulation; size exclusion chromatography; chemical cross-linking; temperature-dependent NMR The FEBS journal High 34837346
2022 RBM3 interacts with Raptor to regulate the autophagy pathway in cardiomyocytes; RBM3 downregulation inhibits autophagy and promotes apoptosis under ischemia-reperfusion conditions. Co-immunoprecipitation confirming RBM3-Raptor interaction; RBM3 knockdown; autophagy and apoptosis assays in I/R model Journal of physiology and biochemistry Medium 36192581
2023 RBM3 has a binding relationship with SLC7A11 mRNA; sodium butyrate promotes RBM3 expression, which indirectly downregulates SLC7A11, thereby promoting ferroptosis in endometrial cancer cells. RNA pulldown and mass spectrometry; transcriptome analysis; metabolome analysis; overexpression; subcutaneous xenograft model Apoptosis Medium 37170022
2023 RBM3 cold induction is regulated by a poison exon within the RBM3 gene whose temperature-dependent inclusion targets mRNA for nonsense-mediated decay; HNRNPH1 mediates cold-dependent exon skipping via its thermosensitive interaction with a G-rich motif within the poison exon; ASO-mediated exclusion of the poison exon raises RBM3 levels at normothermia and provides neuroprotection in prion-diseased mice. Genome-wide CRISPR-Cas9 KO screen in iPSC-derived neurons; splicing analysis; HNRNPH1 KO; ASO treatment; mouse prion disease model; neuronal loss and spongiosis quantification The EMBO journal / EMBO molecular medicine High 36946385 37248947
2023 RBM3 upregulates N6-methyladenosine (m6A) methylation on CTNNB1 (β-catenin) mRNA in a METTL3-dependent manner, decreasing CTNNB1 mRNA stability and inactivating Wnt signaling, thereby inhibiting stemness remodeling of prostate cancer cells in the bone microenvironment. m6A methylation analysis; METTL3 dependence assay; RBM3 overexpression/silencing; co-culture with osteoblasts; Wnt signaling reporter Cell death & disease Medium 36750551
2023 RBM3 interacts with GAS6 mRNA to stabilize it, activating the Nrf2 signaling pathway and providing neuroprotection against acute brain injury. RNA immunoprecipitation assay; RBM3 overexpression; in vivo cerebral injury rat model; oxidative stress and apoptosis assays Neuroscience Medium 38555015
2021 MZF1 acts as a transcription factor for RBM3, binding the RBM3 promoter (confirmed by ChIP and dual-luciferase assay) and promoting RBM3 transcription; this MZF1-RBM3 axis protects against oxidative stress and apoptosis in neuronal cells. ChIP assay; dual-luciferase reporter assay; MZF1 overexpression; RBM3 siRNA knockdown; oxidative stress and apoptosis assays The Journal of toxicological sciences Medium 34602532
2021 RBM3 intrinsically suppresses lung innate lymphoid cell (ILC) activation and type 2/17 inflammation; Rbm3−/− ILCs from bone marrow chimeric mice show increased cytokine production; RBM3-deficient ILCs have increased expression of CysLT1R, and double-KO of Rbm3 and Cyslt1r reduces ST2+IL-17+ ILC accumulation, showing dependence on CysLT1R for part of RBM3's suppressive function. Rbm3−/− mice; Rbm3−/−Rag2−/− mice; bone marrow chimeric mice; allergen challenge model; RNA-seq of Rbm3−/− ILCs; double KO with Cyslt1r Nature communications High 35908044
2022 RBM3 overexpression promotes AKT phosphorylation and enhances glucose metabolism and reduces apoptosis in skeletal muscle under cold exposure; O-GlcNAcylation of NF-κB p65 (mediated by OGT) upregulates RBM3, and OGT-specific skeletal muscle KO mice show decreased RBM3 and p65 phosphorylation, confirming the OGT-p65-RBM3-AKT axis. RBM3 overexpression in C2C12; OGT KO mice; wortmannin AKT inhibition; Western blot; glycolysis and apoptosis assays Cell stress & chaperones Medium 36149580
2017 FAK/Src signaling axis regulates cold-induced RBM3 gene transcription; FAK-specific inhibitor or FAK/Src siRNA silencing significantly abrogates hypothermia-induced RBM3 expression and blocks neuroprotective effects of mild hypothermia against rotenone. Pharmacological inhibitors of multiple signaling pathways; siRNA knockdown of FAK and Src; RT-PCR and Western blot for RBM3; cell viability assay Biochemical and biophysical research communications Medium 33272569
2024 RBM3 stabilizes SOX11 mRNA, increasing its protein expression and promoting neuronal differentiation of human neural stem cells under mild hypothermia (35°C); identified by single-cell RNA sequencing and validated functionally. Single-cell RNA sequencing; RBM3 overexpression/knockdown; mRNA stability assay; in vitro and in vivo NSC transplantation; neuronal differentiation assay iScience Medium 38523796
2021 RBM3 binds MMP9 mRNA (confirmed by RNA immunoprecipitation) and increases MMP9 mRNA stability in pulmonary microvascular endothelial cells, increasing cell permeability; RBM3 also reduces LPS-induced apoptosis possibly by suppressing p53 expression. RNA immunoprecipitation (RIP assay); actinomycin D mRNA stability assay; RBM3 overexpression/knockdown via lentivirus; cell permeability and tight junction assays The Journal of surgical research Medium 33460967
2023 RBM3 binds mRNAs in skeletal muscle predominantly at the junction between the coding region and 3'UTR (identified 14-nucleotide motif); bound transcripts are enriched for contractile apparatus, translation initiation, and proteasome complex gene sets, including Myh1, Eif4b, and Trim63. RNA immunoprecipitation followed by RNA sequencing (RIP-seq); gene set enrichment analysis; motif scanning; network analysis Physiological reports Medium 36750123
2024 RBM3 overexpression promotes mitochondrial metabolism, cellular proliferation, and differentiation of myoblasts; proteomic analysis of RBM3-overexpressing C2C12 cells shows enrichment of fatty acid metabolism, RNA metabolism, and electron transport chain pathways; RBM3 is necessary for enhanced differentiation and maintenance of mitochondrial metabolism during hypothermic preconditioning. Hypothermic preconditioning; RBM3 overexpression; proteomic analysis; C2C12 and primary myoblast differentiation assays; mitochondrial metabolism assays Communications biology Medium 38688991

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism. Journal of cell science 216 15075239
2015 RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature 190 25607368
2005 Cold stress-induced protein Rbm3 binds 60S ribosomal subunits, alters microRNA levels, and enhances global protein synthesis. Proceedings of the National Academy of Sciences of the United States of America 189 15684048
1997 Increased transcript level of RBM3, a member of the glycine-rich RNA-binding protein family, in human cells in response to cold stress. Biochemical and biophysical research communications 172 9245737
2016 Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold. Cellular and molecular life sciences : CMLS 171 27147467
2019 The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production. EBioMedicine 147 31235426
2008 Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene 118 18427544
2011 The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection. Neurobiology of disease 107 21527344
1995 RBM3, a novel human gene in Xp11.23 with a putative RNA-binding domain. Human molecular genetics 98 8634703
2000 Decreased expression of mouse Rbm3, a cold-shock protein, in Sertoli cells of cryptorchid testis. The American journal of pathology 94 10793079
2010 The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death. Pediatric research 88 19770690
2007 Two isoforms of the cold-inducible mRNA-binding protein RBM3 localize to dendrites and promote translation. Journal of neurochemistry 87 17403028
2001 A 5' Leader of Rbm3, a Cold Stress-induced mRNA, Mediates Internal Initiation of Translation with Increased Efficiency under Conditions of Mild Hypothermia. The Journal of biological chemistry 87 11470798
2019 RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury. Nature communications 76 31484925
2006 Positive correlation between the expression of X-chromosome RBM genes (RBMX, RBM3, RBM10) and the proapoptotic Bax gene in human breast cancer. Journal of cellular biochemistry 72 16552754
2013 Effects of moderate and deep hypothermia on RNA-binding proteins RBM3 and CIRP expressions in murine hippocampal brain slices. Brain research 70 23415676
2011 Widespread regulation of miRNA biogenesis at the Dicer step by the cold-inducible RNA-binding protein, RBM3. PloS one 66 22145045
2009 Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 64 19734850
2017 RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3. Current biology : CB 63 28238655
2003 The internal ribosome entry site (IRES) contained within the RNA-binding motif protein 3 (Rbm3) mRNA is composed of functionally distinct elements. The Journal of biological chemistry 58 12824175
2015 Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons. Neuroscience 56 26265550
2015 Cold-inducible RBM3 inhibits PERK phosphorylation through cooperation with NF90 to protect cells from endoplasmic reticulum stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 54 26472337
2011 RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Translational oncology 49 21804916
2023 Sodium butyrate induces ferroptosis in endometrial cancer cells via the RBM3/SLC7A11 axis. Apoptosis : an international journal on programmed cell death 48 37170022
2013 Stress-response protein RBM3 attenuates the stem-like properties of prostate cancer cells by interfering with CD44 variant splicing. Cancer research 48 23667174
2011 Enhanced survival of skeletal muscle myoblasts in response to overexpression of cold shock protein RBM3. American journal of physiology. Cell physiology 47 21593448
2016 RBM3 regulates temperature sensitive miR-142-5p and miR-143 (thermomiRs), which target immune genes and control fever. Nucleic acids research 46 26825461
2017 RNA-binding protein RBM3 prevents NO-induced apoptosis in human neuroblastoma cells by modulating p38 signaling and miR-143. Scientific reports 45 28134320
2011 High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagnostic pathology 43 21955582
2018 Cold-induced protein RBM3 orchestrates neurogenesis via modulating Yap mRNA stability in cold stress. The Journal of cell biology 42 30037926
2015 RNA binding protein RBM3 increases β-catenin signaling to increase stem cell characteristics in colorectal cancer cells. Molecular carcinogenesis 40 26331352
2017 Cold-Inducible Protein RBM3 Protects UV Irradiation-Induced Apoptosis in Neuroblastoma Cells by Affecting p38 and JNK Pathways and Bcl2 Family Proteins. Journal of molecular neuroscience : MN 34 28831692
2008 Identification of cold-shock protein RBM3 as a possible regulator of skeletal muscle size through expression profiling. American journal of physiology. Regulatory, integrative and comparative physiology 32 18753264
2023 ASO targeting RBM3 temperature-controlled poison exon splicing prevents neurodegeneration in vivo. EMBO molecular medicine 29 36946385
2019 The RNA-Binding Protein RBM3 Promotes Neural Stem Cell (NSC) Proliferation Under Hypoxia. Frontiers in cell and developmental biology 29 31824945
2019 Robust RBM3 and β-klotho expression in developing neurons in the human brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 28 31566073
2019 Cold-inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling. Journal of cellular and molecular medicine 27 31436914
2011 Generation of mice deficient in RNA-binding motif protein 3 (RBM3) and characterization of its role in innate immune responses and cell growth. Biochemical and biophysical research communications 26 21684257
2023 RBM3 suppresses stemness remodeling of prostate cancer in bone microenvironment by modulating N6-methyladenosine on CTNNB1 mRNA. Cell death & disease 25 36750551
2021 TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection. Life science alliance 25 33563652
2019 LINC00096 Promotes the Proliferation and Invasion by Sponging miR-383-5p and Regulating RBM3 Expression in Triple-Negative Breast Cancer. OncoTargets and therapy 25 31819536
2021 Long non‑coding RNA MIR4435‑2HG promotes the progression of head and neck squamous cell carcinoma by regulating the miR‑383‑5p/RBM3 axis. Oncology reports 23 33846802
2020 Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome. Brain communications 23 33585816
2017 TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3. Scientific reports 23 28536481
2019 Regulating glycolysis, the TLR4 signal pathway and expression of RBM3 in mouse liver in response to acute cold exposure. Stress (Amsterdam, Netherlands) 22 30821572
2018 Infants Uniquely Express High Levels of RBM3 and Other Cold-Adaptive Neuroprotectant Proteins in the Human Brain. Developmental neuroscience 22 30399610
2018 RNA binding motif protein 3 (RBM3) drives radioresistance in nasopharyngeal carcinoma by reducing apoptosis via the PI3K/AKT/Bcl-2 signaling pathway. American journal of translational research 22 30662656
2019 RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression. International journal of oncology 21 30720048
2018 RBM3 expression is upregulated by NF-κB p65 activity, protecting cells from apoptosis, during mild hypothermia. Journal of cellular biochemistry 21 29388696
2023 HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion. The EMBO journal 20 37248947
2018 Hypothermia-induced RNA-binding motif protein 3 (RBM3) stimulates osteoblast differentiation via the ERK signaling pathway. Biochemical and biophysical research communications 20 29505791
2018 Cold shock protein RBM3 attenuates atrophy and induces hypertrophy in skeletal muscle. Journal of muscle research and cell motility 20 30051360
2017 Expression of RNA-binding Motif Protein 3 (RBM3) and Cold-inducible RNA-binding protein (CIRP) Is Associated with Improved Clinical Outcome in Patients with Colon Cancer. Anticancer research 20 28373441
2017 Stress Response Protein RBM3 Promotes the Development of Colitis-associated Cancer. Inflammatory bowel diseases 19 27930406
2017 High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer. PloS one 19 28800641
2020 Role of RBM3 in the regulation of cell proliferation in hepatocellular carcinoma. Experimental and molecular pathology 18 32976820
2020 The overexpression of RBM3 alleviates TBI-induced behaviour impairment and AD-like tauopathy in mice. Journal of cellular and molecular medicine 17 32648620
2020 The mRNA-Binding Protein RBM3 Regulates Activity Patterns and Local Synaptic Translation in Cultured Hippocampal Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 33310754
2016 Cellular Functions of RNA-Binding Motif Protein 3 (RBM3): Clues in Hypothermia, Cancer Biology and Apoptosis. Protein and peptide letters 17 27364162
2023 RBM3 is associated with acute lung injury in septic mice and patients via the NF-κB/NLRP3 pathway. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 16 36781430
2022 RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia. Journal of cellular physiology 16 35926117
2018 Cold Shock Induced Protein RBM3 but Not Mild Hypothermia Protects Human SH-SY5Y Neuroblastoma Cells From MPP+-Induced Neurotoxicity. Frontiers in neuroscience 16 29773975
2017 Evidence towards RNA Binding Motif (RNP1, RRM) Protein 3 (RBM3) as a Potential Biomarker of Lithium Response in Bipolar Disorder Patients. Journal of molecular neuroscience : MN 16 28616776
2000 Capture of cytokine-responsive genes (NACA and RBM3) using a gene trap approach. Blood 15 10845906
2017 Translational study reveals a two-faced role of RBM3 in pancreatic cancer and suggests its potential value as a biomarker for improved patient stratification. Oncotarget 14 29464064
2022 RNA-binding protein RBM3 intrinsically suppresses lung innate lymphoid cell activation and inflammation partially through CysLT1R. Nature communications 13 35908044
2022 RNA binding motif protein 3 (RBM3) promotes protein kinase B (AKT) activation to enhance glucose metabolism and reduce apoptosis in skeletal muscle of mice under acute cold exposure. Cell stress & chaperones 12 36149580
2020 Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer. Cancer medicine 12 32491279
2020 Expression regulation of cold-inducible protein RBM3 by FAK/Src signaling for neuroprotection against rotenone under mild hypothermia. Biochemical and biophysical research communications 12 33272569
2019 RBM3 and CIRP expressions in targeted temperature management treated cardiac arrest patients-A prospective single center study. PloS one 11 31821351
2014 Spatiotemporal profile and essential role of RBM3 expression after spinal cord injury in adult rats. Journal of molecular neuroscience : MN 11 24668366
2019 Prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers. Journal of cancer research and clinical oncology 10 30758670
2017 Neuroprotection via RNA-binding protein RBM3 expression is regulated by hypothermia but not by hypoxia in human SK-N-SH neurons. Hypoxia (Auckland, N.Z.) 10 28580361
2022 Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression. Apoptosis : an international journal on programmed cell death 9 35930183
2021 RBM3 Increases Cell Survival but Disrupts Tight Junction of Microvascular Endothelial Cells in Acute Lung Injury. The Journal of surgical research 9 33460967
2020 Cold-inducible RNA-binding protein Cirp, but not Rbm3, may regulate transcript processing and protection in tissues of the hibernating ground squirrel. Cell stress & chaperones 9 32307648
2020 CRISPR/Cas9 Editing of the C. elegans rbm-3.2 Gene using the dpy-10 Co-CRISPR Screening Marker and Assembled Ribonucleoprotein Complexes. Journal of visualized experiments : JoVE 9 33369608
2020 Skeletal muscle RBM3 expression is associated with extended lifespan in Ames Dwarf and calorie restricted mice. Experimental gerontology 9 33385482
2024 Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway. iScience 8 38523796
2021 PRR11 unveiled as a top candidate biomarker within the RBM3-regulated transcriptome in pancreatic cancer. The journal of pathology. Clinical research 8 34379360
2021 MZF1 alleviates oxidative stress and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription. The Journal of toxicological sciences 8 34602532
2021 Structural and dynamic studies of the human RNA binding protein RBM3 reveals the molecular basis of its oligomerization and RNA recognition. The FEBS journal 8 34837346
2018 Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome. BMC cancer 8 30419865
2014 Molecular characterization of RNA binding motif protein 3 (RBM3) gene from Pashmina goat. Research in veterinary science 8 25544695
2024 RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway. Current molecular pharmacology 6 39041256
2021 Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumors. Journal of surgical oncology 6 33497473
2021 Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma. Annals of translational medicine 6 33569425
2024 RBM3 Accelerates Wound Healing of Skin in Diabetes through ERK1/2 Signaling. Current molecular pharmacology 5 37982286
2024 Cold-shock proteome of myoblasts reveals role of RBM3 in promotion of mitochondrial metabolism and myoblast differentiation. Communications biology 5 38688991
2023 The transcript interactome of skeletal muscle RNA binding protein motif 3 (RBM3). Physiological reports 5 36750123
2023 Chronic social stress blunts core body temperature and molecular rhythms of Rbm3 and Cirbp in mouse lateral habenula. Open biology 5 37463657
2019 Mild hypothermia promotes the viability of in vitro-produced bovine blastocysts and their transcriptional expression of the cold-inducible transcription factor Rbm3 during in vitro culture. The Journal of reproduction and development 5 30905884
2024 RBM3 Ameliorates Acute Brain Injury-induced Inflammation and Oxidative Stress by Stabilizing GAS6 mRNA Through Nrf2 Signaling Pathway. Neuroscience 4 38555015
2022 Pre-clinical and clinical studies on the role of RBM3 in muscle-invasive bladder cancer: longitudinal expression, transcriptome-level effects and modulation of chemosensitivity. BMC cancer 4 35109796
2022 RBM3 interacts with Raptor to regulate autophagy and protect cardiomyocytes from ischemia-reperfusion-induced injury. Journal of physiology and biochemistry 4 36192581
2020 Characterization of RNA-Binding Motif 3 (RBM3) Protein Levels and Nuclear Architecture Changes in Aggressive and Recurrent Prostate Cancer. Cancer reports (Hoboken, N.J.) 4 32587951
2023 Characterization of Circulating Cold Shock Proteins FGF21 and RBM3 in a Multi-Center Study of Pediatric Cardiac Arrest. Therapeutic hypothermia and temperature management 3 37669029
2025 Therapeutic modulation of protein RBM3 for ischemic stroke treatment. Frontiers in pharmacology 2 40124786
2025 Hypothermia Alleviates TBI-Induced Tau Hyperphosphorylation Through RBM3-Dependent GSK-3β and AMPK Pathways. Neurocritical care 2 40457153
2024 Cold shock proteins CIRBP and RBM3 may indicate hypothermia death: A case report. Journal of forensic and legal medicine 2 39550904