Affinage

RBM3

RNA-binding protein 3 · UniProt P98179

Length
157 aa
Mass
17.2 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM3 is a cold-shock RNA-binding protein that acts as a master post-transcriptional effector of the hypothermic response, coupling temperature sensing to selective control of mRNA stability, translation, and splicing to produce neuroprotection, regulate the cell cycle, and modulate cancer cell behavior (PMID:25607368, PMID:15684048). Its own induction during cooling is controlled at multiple levels: a temperature-sensitive poison exon whose cold-dependent skipping (mediated by HNRNPH1 binding a G-rich motif) determines RBM3 levels and is the sole driver of cold-induced expression (PMID:37248947, PMID:36946385); an internal ribosome entry site in the 5' leader that supports cap-independent translation enhanced at mild hypothermia (PMID:11470798, PMID:12824175); and transcriptional activation through converging FAK/Src, TrkB-PLCγ1-CREB, and NF-κB p65 signaling that feed into the RBM3 promoter (PMID:33272569, PMID:33563652, PMID:29388696). Once expressed, RBM3 associates with 40S and 60S ribosomal subunits and globally increases protein synthesis, and it promotes Dicer-dependent processing of pre-miRNA intermediates (PMID:15684048, PMID:12824175, PMID:22145045). Through its N-terminal RRM domain, which adopts a βαββαβ fold and engages RNA via its β-sheet and loops, RBM3 binds and stabilizes numerous target mRNAs—including RTN3, Yap1, SOX11, and MEF2C—to drive synapse regeneration, neuronal differentiation, and barrier integrity (PMID:34837346, PMID:28238655, PMID:30037926, PMID:38523796, PMID:38670534), and the RRM alone is sufficient to direct alternative splice-site selection genome-wide (PMID:39387568). RBM3 also functions through protein partners, cooperating with NF90 to suppress PERK-eIF2α ER stress signaling and with IMP2 to stimulate IGF2 release for neurogenesis (PMID:26472337, PMID:31484925). These activities make RBM3 a mediator of hypothermic neuroprotection: it is required for cooling-induced synapse reassembly and survival in prion and 5XFAD mouse models, and ASO-driven removal of its poison exon delivers sustained neuroprotection at normothermia (PMID:25607368, PMID:37248947, PMID:36946385).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2001 High

    Established how RBM3 protein rises during cooling despite global translational repression, identifying a cap-independent translation mechanism for its own mRNA.

    Evidence Dicistronic reporter assays and 5'-leader mutagenesis in cells and cell-free lysates showing a hypothermia-enhanced IRES

    PMID:11470798

    Open questions at the time
    • Trans-acting factors mediating temperature sensitivity not identified
    • Quantitative contribution of IRES versus transcription to total induction unresolved
  2. 2003 High

    Dissected the RBM3 IRES into discrete modules and showed a 22-nt element directly binds 40S subunits, defining the cis-architecture of cap-independent translation.

    Evidence IRES deletion/mutational analysis with 40S ribosomal subunit binding and cytoplasmic protein binding assays

    PMID:12824175

    Open questions at the time
    • Identities of the element-specific cytoplasmic proteins not determined
    • Link to temperature regulation not mechanistically closed
  3. 2004 High

    Showed RBM3 induction by environmental stress is transcriptional and HIF-1/mitochondria-independent, distinguishing it from canonical hypoxia responses.

    Evidence Nuclear run-on and actinomycin-D assays in HIF-1-deficient and mitochondria-depleted cells

    PMID:15075239

    Open questions at the time
    • Responsible transcription factor not identified in this study
    • Promoter elements not mapped
  4. 2005 High

    Demonstrated RBM3 functionally enhances global translation and associates with ribosomes, linking it to protein synthesis output.

    Evidence Stable overexpression in N2a cells with [35S]-Met incorporation, sucrose gradient sedimentation, and RNA-independent 60S association

    PMID:15684048

    Open questions at the time
    • Mechanism connecting ribosome binding to enhanced translation unresolved
    • Specificity for particular transcripts not addressed
  5. 2007 Medium

    Connected RBM3 isoforms to dendritic localization and polysome formation, implicating RBM3 in neuronal translation.

    Evidence Polysome profiling, immunofluorescence, and translation assays of two spliced isoforms in neuronal cell lines

    PMID:17403028

    Open questions at the time
    • Functional significance of the single-arginine difference unclear
    • Post-translational modifications not mapped to function
  6. 2008 Medium

    Linked RBM3 to mRNA stabilization of specific oncogenic transcripts and to cell-cycle integrity, showing loss triggers mitotic catastrophe.

    Evidence siRNA knockdown and overexpression with mRNA stability assays, cell-cycle marker blots, and xenograft growth

    PMID:18427544

    Open questions at the time
    • Direct RBM3-target mRNA binding not demonstrated here
    • Mechanism of cyclin B1/Cdc25c dysregulation indirect
  7. 2011 High

    Defined a role for RBM3 in miRNA biogenesis, showing it promotes Dicer processing of pre-miRNAs and broadly sustains miRNA levels.

    Evidence Direct pre-miRNA binding, Dicer activity and export assays, and genome-wide miRNA profiling under RBM3 knockdown/overexpression

    PMID:22145045

    Open questions at the time
    • Structural basis of pre-miRNA recognition not defined
    • Relationship between miRNA modulation and translation enhancement not integrated
  8. 2011 Medium

    Established RBM3 as a causal mediator of hypothermic neuroprotection and as a G2-phase cell-cycle regulator using loss- and gain-of-function.

    Evidence siRNA/overexpression with PARP, DNA fragmentation, and LDH assays in neurons; flow cytometry of Rbm3-/- MEFs

    PMID:21527344 PMID:21684257

    Open questions at the time
    • Molecular targets mediating neuroprotection not yet identified
    • G2 control mechanism not mechanistically linked to RNA targets
  9. 2013 Medium

    Showed RBM3 regulates stress-responsive alternative splicing of CD44, extending its activity beyond mRNA stability into splice-isoform control.

    Evidence Overexpression/knockdown with CD44 isoform RT-PCR, soft-agar and in vivo tumor assays in prostate cancer cells

    PMID:23667174

    Open questions at the time
    • Direct splicing mechanism not demonstrated at this stage
    • Whether effect is direct or via cofactors unresolved
  10. 2015 High

    Demonstrated in vivo that RBM3 drives cooling-induced synapse regeneration and rescues neurodegeneration, establishing therapeutic relevance.

    Evidence Lentiviral overexpression and shRNA in prion and 5XFAD mice with synapse counting, behavior, and survival

    PMID:25607368

    Open questions at the time
    • Downstream effector mRNAs not identified in this study
    • Mechanism of synapse reassembly left open
  11. 2015 High

    Identified RBM3-NF90 cooperation as a brake on PERK-eIF2α-CHOP ER stress signaling, linking RBM3 to proteostasis defense.

    Evidence AP-MS, reciprocal Co-IP, proximity ligation, and KO hippocampal slices under ER stress induction

    PMID:26472337

    Open questions at the time
    • RNA dependence of the interaction not molecularly defined
    • Direct PERK inhibition mechanism not resolved
  12. 2017 High

    Identified RTN3 as a direct RBM3 mRNA target and downstream neuroprotective effector, providing a molecular chain for synapse protection.

    Evidence Translatome profiling, RBM3 KD/OE, direct RNA binding, and in vivo RTN3 shRNA and overexpression rescue

    PMID:28238655

    Open questions at the time
    • How RTN3 mechanistically protects synapses not fully resolved
    • Additional parallel effectors not excluded
  13. 2018 Medium

    Mapped upstream transcriptional control of RBM3, defining NF-κB p65 (Ser276) promoter binding and ERK/p38 signaling in differentiation contexts.

    Evidence p65 ChIP on RBM3 promoter with CAPE inhibition and rescue; ERK/p38 inhibitor and Runx2 readouts in osteoblasts

    PMID:29388696 PMID:29505791

    Open questions at the time
    • How cooling activates p65 phosphorylation unresolved
    • ERK-Runx2 link to RNA-binding activity not established
  14. 2019 Medium

    Expanded RBM3's direct mRNA target set (Yap1, IGF2/IMP2 axis) and showed niche-dependent control of neurogenesis and neuronal differentiation.

    Evidence Co-IP with IMP2, 3'UTR binding to Yap1, KO mice under cold stress, and zone-specific NSC assays with rescue

    PMID:30037926 PMID:31484925

    Open questions at the time
    • Basis of niche specificity (SGZ vs SVZ) unexplained
    • Direct versus indirect mRNA stabilization not always separated
  15. 2019 Low

    Implicated RBM3 in cancer phenotypes through stabilization of ARPC2 and SLC7A11 mRNAs, affecting metastasis and ferroptosis.

    Evidence RNA pull-down/RIP with mass spectrometry, RBM3 OE/KD, and proliferation/ferroptosis and xenograft readouts

    PMID:30720048 PMID:37170022

    Open questions at the time
    • ARPC2 binding rests on a single RNA pull-down without full rescue
    • Direct versus indirect regulation of SLC7A11 not firmly established
  16. 2020 Medium

    Refined RBM3's translational role to the synaptic compartment, showing it controls local but not global translation in hippocampal neurons.

    Evidence Knockdown with STED imaging, synaptic vesicle imaging, and local translation assays in rat neurons

    PMID:33310754

    Open questions at the time
    • Local mRNA targets at synapses not enumerated
    • Reconciliation with global translation enhancement reports unresolved
  17. 2021 High

    Defined the TrkB-PLCγ1-CREB signaling route inducing RBM3 and an RBM3-DUSP6 negative feedback loop, and provided the first RRM structure with RNA-binding interface and cold-favored oligomerization.

    Evidence Pharmacological/genetic epistasis with TrkB agonist in vivo; solution NMR structure with RNA titration, MD, and cross-linking

    PMID:33563652 PMID:34837346

    Open questions at the time
    • Functional role of cold-favored oligomerization not directly demonstrated
    • Connection between RRM structure and specific target selection open
  18. 2021 Medium

    Connected RBM3 to oncogenic Wnt/β-catenin activation and identified MZF1 as a direct transcriptional activator of RBM3.

    Evidence TCF/LEF reporters, β-catenin fractionation, GSK3β inhibitor in CRC cells; MZF1 ChIP and reporter with RBM3-siRNA rescue

    PMID:26331352 PMID:34602532

    Open questions at the time
    • How RBM3 inactivates GSK3β mechanistically unclear
    • Whether β-catenin effect is direct mRNA-mediated not shown
  19. 2021 Low

    Extended RBM3 mRNA-stabilization activity to MMP9 in endothelial permeability and to Raptor-mediated autophagy in cardiomyocytes.

    Evidence RIP and actinomycin D stability assays for MMP9; Co-IP with Raptor and autophagy/apoptosis readouts in I/R

    PMID:33460967 PMID:36192581

    Open questions at the time
    • Raptor interaction rests on a single Co-IP without reciprocal validation
    • Mechanism of p53 suppression by RBM3 unresolved
  20. 2023 High

    Identified the temperature-sensitive poison exon and HNRNPH1 as the core thermosensor governing cold-induced RBM3 expression, and validated ASO exclusion as a normothermic neuroprotective strategy.

    Evidence Genome-wide CRISPR screen in iPSC neurons, HNRNPH1 KO/KD, structural G-rich motif analysis, poison-exon deletion, and ASO in prion mice

    PMID:36946385 PMID:37248947

    Open questions at the time
    • How HNRNPH1 itself senses temperature not fully resolved
    • Interplay between poison-exon control and IRES/transcriptional inputs not integrated
  21. 2023 Medium

    Showed RBM3 can act as a tumor suppressor via m6A-dependent destabilization of CTNNB1, opposing Wnt-driven stemness in prostate cancer.

    Evidence Osteoblast co-culture, m6A assays on CTNNB1 with METTL3 dependence, mRNA stability, and stemness markers

    PMID:36750551

    Open questions at the time
    • How RBM3 couples to METTL3-mediated m6A deposition unclear
    • Reconciliation with pro-Wnt CRC findings not addressed
  22. 2024 Medium

    Established RBM3 as a genome-wide alternative-splicing regulator whose RRM domain alone directs splice-site selection, mechanistically grounding earlier splicing observations.

    Evidence RNA-seq of Rbm3-deficient cells with cDNA rescue and MS2 tethering between competing 5' splice sites with RRM truncation

    PMID:39387568

    Open questions at the time
    • Sequence determinants of splice-site target selection not defined
    • Relationship between splicing role and mRNA-stabilization role not unified
  23. 2024 Medium

    Broadened RBM3's stabilized-target repertoire (SOX11, MEF2C, GAS6) and metabolic functions, linking it to neuronal differentiation, BBB integrity, antioxidant signaling, and myoblast mitochondrial metabolism.

    Evidence RIP and mRNA stability assays, scRNA-seq, in vivo injury models, and proteomic/metabolic profiling in NSCs, endothelial cells, and myoblasts

    PMID:38523796 PMID:38555015 PMID:38670534 PMID:38688991

    Open questions at the time
    • GAS6 regulation rests on a single RIP assay
    • Whether metabolic effects are direct mRNA-mediated or downstream not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RBM3's distinct biochemical activities—ribosome association, target-mRNA stabilization, splice-site selection, and pre-miRNA processing—are coordinated and directed to specific transcripts via a single RRM remains unresolved.
  • No unified model linking RRM-based RNA recognition to target selectivity across functions
  • Context-dependent tumor-suppressive versus oncogenic roles unreconciled
  • Direct genome-wide binding map (e.g. CLIP) not present in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0045182 translation regulator activity 4 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 2
Partners
HNRNPH1IMP2METTL3NF90PI3K P85RAPTOR

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The 5' leader of Rbm3 mRNA contains an internal ribosome entry site (IRES) that mediates cap-independent translation; activity of this IRES is enhanced up to 5-fold at mild hypothermia (33°C) compared to 37°C, explaining increased Rbm3 protein levels despite global translational repression during cooling. Dicistronic reporter mRNA assays in transfected cells and cell-free lysates; deletion/mutational analysis of the 5' leader The Journal of biological chemistry High 11470798
2003 The Rbm3 mRNA IRES is highly modular, comprising at least 9 discrete cis-acting sequences including a 22-nt IRES module that directly binds 40S ribosomal subunits, a 10-nt enhancer, and 2 inhibitory sequences; distinct cytoplasmic proteins bind each cis-acting element. Deletion and mutational analysis of IRES; binding studies with 40S ribosomal subunits; cytoplasmic protein binding assays The Journal of biological chemistry High 12824175
2005 RBM3 overexpression causes a ~3-fold increase in global protein synthesis at both 37°C and 32°C; a fraction of RBM3 associates with 60S ribosomal subunits in an RNA-independent manner; RBM3 expression reduces the levels of a microRNA-containing complex that sediments between the top of sucrose gradients and 40S subunits, suggesting RBM3 enhances translation by modulating microRNA levels. Stable overexpression of c-Myc-tagged Rbm3 in N2a cells; [35S]-methionine incorporation assay; sucrose gradient sedimentation; RNA-independent ribosome association assay Proceedings of the National Academy of Sciences of the United States of America High 15684048
2004 RBM3 and CIRP mRNA upregulation by hypoxia is regulated at the level of gene transcription (shown by actinomycin-D inhibition and nuclear run-on assays), via a mechanism independent of HIF-1 and mitochondria. Nuclear run-on assays; actinomycin-D treatment; HIF-1α/β-deficient cell lines; mitochondria-depleted cells; respiratory chain inhibitors Journal of cell science High 15075239
2007 Two alternatively spliced RBM3 isoforms differing by a single arginine residue localize to neuronal dendrites; both are post-translationally modified. Overexpression of either isoform enhances global translation, formation of active polysomes, and activation of initiation factors in neuronal cell lines. The isoform lacking the spliced arginine shows higher dendritic localization and is the only isoform present in astrocytes. Sucrose gradient fractionation; immunofluorescence localization; polysome profiling; transfection of neuronal cell lines; identification of post-translational modifications Journal of neurochemistry Medium 17403028
2008 RBM3 overexpression stabilizes COX-2, IL-8, and VEGF mRNAs and enhances their translation; RBM3 knockdown causes loss of translation of these transcripts and induces mitotic catastrophe associated with nuclear cyclin B1 accumulation and phosphorylation of Cdc25c, Chk1, and Chk2. siRNA knockdown; forced overexpression; mRNA stability assays; western blotting for cell cycle regulators; xenograft tumor growth assays Oncogene Medium 18427544
2011 RBM3 is required for the Dicer processing step of miRNA biogenesis: RBM3 directly binds ~70 nt pre-miRNA intermediates and promotes their association with active Dicer complexes, overcoming an intrinsic inhibitory influence on pre-miRNP processing; knockdown of RBM3 downregulates >60% of detectable miRNAs without affecting primary transcript levels or Dicer activity itself. miRNA array; Northern blot; PCR; RBM3 knockdown/overexpression; mild hypothermia induction; mechanistic assays for Dicer activity and pre-miRNA cytoplasmic transport; direct binding of RBM3 to pre-miRNA intermediates PloS one High 22145045
2011 RBM3 knockdown in neural cells significantly diminishes hypothermia-induced neuroprotection; vector-driven RBM3 overexpression reduces PARP cleavage, prevents internucleosomal DNA fragmentation, and reduces LDH release in the absence of hypothermia, establishing RBM3 as a mediator of hypothermic neuroprotection in neurons. siRNA knockdown; vector overexpression; PARP cleavage assay; DNA fragmentation assay; LDH release assay in primary neurons, PC12 cells, and organotypic slice cultures Neurobiology of disease Medium 21527344
2011 RBM3 knockout MEFs show markedly increased G2-phase accumulation compared to wild-type MEFs, revealing a role for RBM3 in G2-phase cell cycle control. Generation of Rbm3-/- mice; cell cycle analysis of mouse embryonic fibroblasts by flow cytometry Biochemical and biophysical research communications Medium 21684257
2013 RBM3 overexpression or culturing cells at 32°C suppresses alternative RNA splicing of CD44 variant v8-v10 and increases expression of standard CD44s isoform in prostate cancer cells; conversely, RBM3 silencing or soft-agar culture increases the CD44v8-v10:CD44s mRNA ratio, linking RBM3 to stress-regulated alternative splicing of CD44. RBM3 overexpression and siRNA knockdown; RT-PCR for CD44 isoforms; soft-agar culture; in vivo tumor growth assay Cancer research Medium 23667174
2015 RBM3 deficiency in mouse models of neurodegeneration (prion disease and 5XFAD) correlates with failure of synapse regeneration after cooling; RBM3 overexpression (lentiviral or by hypothermia pre-treatment) restores synapse reassembly, prevents behavioral deficits and neuronal loss, and prolongs survival; RBM3 knockdown exacerbates synapse loss and accelerates disease. RBM3 lentiviral overexpression and shRNA knockdown in mouse brain; synapse counting; behavioral testing; survival analysis in prion and 5XFAD mouse models Nature High 25607368
2015 RBM3 inhibits PERK phosphorylation and attenuates the PERK-eIF2α-CHOP ER stress pathway; this occurs through RBM3's cooperation with NF90, which is a novel PERK-interacting protein; RBM3's interaction with NF90 is RNA-dependent and is required for regulation of PERK activity. RBM3 knockout hippocampal slice cultures; siRNA knockdown and overexpression in HEK293 cells; thapsigargin/tunicamycin ER stress induction; affinity purification with mass spectrometry; co-immunoprecipitation; proximity ligation assay FASEB journal High 26472337
2017 RTN3 is a downstream effector of RBM3 neuroprotection: RBM3 directly binds RTN3 mRNA and drives its increased expression during cooling; RTN3 knockdown eliminates cooling-induced neuroprotection in mice; lentiviral RTN3 overexpression prevents synaptic loss and cognitive deficits in a neurodegeneration mouse model independently of RBM3. Translatome profiling; RBM3 KD/OE; RTN3 shRNA in vivo; lentiviral RTN3 overexpression; RNA binding assays; synaptic and behavioral assays Current biology : CB High 28238655
2018 RBM3 overexpression activates ERK and p38 phosphorylation to stimulate osteoblast differentiation; ERK inhibition decreases Runx2 expression downstream of RBM3, placing RBM3 upstream of the ERK-Runx2 axis in osteoblast differentiation. RBM3 overexpression and siRNA knockdown; ERK/p38 inhibitor treatment; osteogenic gene expression (Runx2, OC); mineralization assay Biochemical and biophysical research communications Medium 29505791
2018 Cooling activates NF-κB p65 phosphorylation at Ser276, which then binds to a specific element in the RBM3 gene promoter to transcriptionally activate RBM3 expression; CAPE (NF-κB inhibitor) prevents RBM3 induction and increases apoptosis, which is rescued by RBM3 overexpression. NF-κB p65 chromatin immunoprecipitation of RBM3 promoter; CAPE treatment; RBM3 OE rescue experiments; western blot and RT-PCR Journal of cellular biochemistry Medium 29388696
2018 RBM3 directly interacts with PI3K subunit p85 in NPC cells, and RBM3 overexpression enhances radioresistance through activation of the AKT/Bcl-2 signaling pathway; AKT inhibition attenuates RBM3-mediated radioresistance. Co-immunoprecipitation of RBM3 with PI3K p85; RBM3 KD and OE; AKT inhibitor; apoptosis and survival assays American journal of translational research Low 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 in the subventricular zone (SVZ) of the brain, establishing a niche-dependent RBM3-IMP2-IGF2 signaling pathway that promotes neurogenesis after hypoxic-ischemic injury. Co-immunoprecipitation; lentiviral RBM3 OE/KD in vivo; IGF2 ELISA; NSC proliferation and differentiation assays in SGZ and SVZ Nature communications Medium 31484925
2019 RBM3 binds directly to the 3'UTR of Yap1 mRNA (at seven predicted binding sites) and regulates its stability; RBM3 knockout during cold stress exacerbates neuronal differentiation defects in the embryonic brain, which are partially rescued by YAP1 overexpression. RNA binding motif analysis; 3'UTR binding assays; RBM3 KO mice subjected to maternal cold stress; in utero electroporation rescue with YAP1 OE The Journal of cell biology Medium 30037926
2019 RBM3 binds and stabilizes ARPC2 mRNA via its 3'UTR (RNA pull-down assay), and ARPC2 mediates RBM3-driven breast cancer cell proliferation and metastasis. RNA immunoprecipitation/RNA pull-down; RBM3 KD; ARPC2 KD; proliferation and invasion assays International journal of oncology Low 30720048
2019 RBM3 has a binding relationship with SLC7A11 mRNA (shown by RNA pull-down and mass spectrometry); RBM3 upregulation (induced by sodium butyrate) leads to decreased SLC7A11 expression and promotes ferroptosis in endometrial cancer cells. RNA pull-down with mass spectrometry; RBM3 OE/KD; SLC7A11 expression; ferroptosis markers (ROS, lipid peroxidation, GSH/GSSG); xenograft model Apoptosis Medium 37170022
2020 RBM3 knockdown in hippocampal neurons specifically alters local synaptic translation without affecting global cellular translation; RBM3 levels change over 24 h primarily at synapses and RBM3 knockdown alters synaptic vesicle dynamics and neuronal activity patterns. RBM3 knockdown in rat hippocampal neuron cultures; STED microscopy; synaptic vesicle imaging; local translation assay; 24 h transcriptome analysis The Journal of neuroscience Medium 33310754
2021 Cooling activates TrkB via PLCγ1 and pCREB signaling to induce RBM3 expression; RBM3 in turn negatively feeds back on TrkB-induced ERK activation by inducing its specific phosphatase DUSP6; RBM3-null neurons lose cold-induced structural plasticity; TrkB agonism induces RBM3 without cooling and prevents neurodegeneration. Pharmacological antagonism and genetic reduction of TrkB and downstream mediators; RBM3-null neuron cultures; PLCγ1 and pCREB signaling assays; DUSP6 induction assay; prion disease mouse model with TrkB inhibition; TrkB agonist treatment Life science alliance High 33563652
2021 RBM3 NMR structure of the N-terminal RRM domain (84 residues) reveals a βαββαβ topology; NMR-monitored titrations and MD simulations identify the β-sheet and two loops as the RNA-binding interface; RBM3 forms oligomers in solution via RRM domain interactions that are favored by decreased temperature, potentially linking oligomerization to cold-shock function. Solution NMR structure determination; NMR-monitored RNA titration; molecular dynamics simulations; size exclusion chromatography; chemical cross-linking The FEBS journal High 34837346
2021 RBM3 interacts with MMP9 mRNA (RIP assay) and increases MMP9 mRNA stability, contributing to increased microvascular endothelial cell permeability; RBM3 also reduces LPS-induced apoptosis by suppressing p53 expression. RNA immunoprecipitation (RIP); actinomycin D mRNA stability assay; RBM3 OE/KD stable cell lines; cell permeability assay; p53 western blot The Journal of surgical research Medium 33460967
2022 RBM3 interacts with Raptor (a component of mTORC1) to regulate the autophagy pathway in cardiomyocytes; RBM3 knockdown inhibits autophagy and promotes apoptosis in ischemia-reperfusion conditions. Co-immunoprecipitation of RBM3 with Raptor; RBM3 KD; autophagy markers; apoptosis assay in I/R model Journal of physiology and biochemistry Low 36192581
2023 A poison exon within the RBM3 gene (responsible for nonsense-mediated decay of RBM3 mRNA) is solely responsible for its cold-induced expression; HNRNPH1 mediates cold-dependent skipping of this poison exon via thermosensitive interaction with a G-rich motif within the exon; ASO-mediated exclusion of the poison exon yields high RBM3 levels at normothermia and provides neuroprotection in prion-diseased mice. Genome-wide CRISPR-Cas9 KO screen in RBM3-reporter iPSC-derived neurons; splicing analysis; HNRNPH1 KO/KD; NMR/structural analysis of temperature-sensitive G-rich motif binding; genetic deletion of poison exon; ASO treatment in prion mouse model The EMBO journal High 37248947
2023 A poison exon in the RBM3 gene is solely responsible for cold-induced RBM3 expression; genetic removal or ASO-mediated exclusion of this exon yields sustained high RBM3 levels in mouse brains at normothermia; a single ASO administration provides long-lasting neuroprotection in prion-diseased mice, preventing neuronal loss and spongiosis. Genetic deletion of poison exon; ASO treatment (FDA-approved chemistry); western blot for RBM3; neuropathology in prion mouse model EMBO molecular medicine High 36946385
2023 RBM3 upregulates N6-methyladenosine (m6A) methylation on CTNNB1 mRNA in a manner dependent on the methyltransferase METTL3, resulting in decreased CTNNB1 mRNA stability and inactivation of Wnt/β-catenin signaling; this suppresses osteoblast-induced stemness remodeling of prostate cancer cells. Co-culture with osteoblasts; m6A methylation assay on CTNNB1 mRNA; METTL3 dependence assay; CTNNB1 mRNA stability; Wnt signaling and stemness markers Cell death & disease Medium 36750551
2024 RBM3 deficiency leads to transcriptome-wide pre-mRNA splicing alterations that are reversed by RBM3 re-expression from a cDNA; an MS2 tethering assay shows RBM3 regulates splice site selection when recruited between competing 5' splice sites; the RRM domain alone is sufficient for splicing regulation. RNA-seq of Rbm3-deficient cells; RBM3 cDNA rescue; MS2 tethering assay with competing 5' splice sites; RRM domain truncation RNA biology Medium 39387568
2024 RBM3 binds and stabilizes MEF2C mRNA; MEF2C then binds to the promoters of tight junction proteins ZO-1 and occludin to enhance their transcription; RBM3 downregulation by Aβ1-42 decreases MEF2C/ZO-1/occludin levels and increases blood-brain barrier permeability. RNA immunoprecipitation (RIP) of RBM3-MEF2C mRNA; MEF2C ChIP on ZO-1/occludin promoters; luciferase reporter; RBM3 and MEF2C KD; BBB permeability assay Biochimica et biophysica acta. Molecular cell research Medium 38670534
2024 RBM3 binds and stabilizes GAS6 mRNA (shown by RNA immunoprecipitation) and thereby activates Nrf2 signaling to reduce oxidative stress and inflammation in acute brain injury models; RBM3 overexpression reduces neurological deficits in a rat cerebral injury model. RNA immunoprecipitation (RIP) of RBM3-GAS6 mRNA; RBM3 OE in vivo and in vitro; Nrf2 pathway assays; behavioral and histological readouts Neuroscience Low 38555015
2024 RBM3 promotes mitochondrial metabolism and myoblast differentiation; RBM3 overexpression at 37°C is sufficient to enhance mitochondrial metabolism, cellular proliferation, and differentiation of C2C12 and primary myoblasts; proteomic analysis shows RBM3 OE enriches pathways of fatty acid metabolism, RNA metabolism, and electron transport chain. Cold-shock proteomics; RBM3 OE/KD in C2C12 and primary myoblasts; mitochondrial metabolism assays; differentiation assays; quantitative proteomics Communications biology Medium 38688991
2024 Mild hypothermia (35°C) promotes neuronal differentiation of human neural stem cells via RBM3; RBM3 stabilizes SOX11 mRNA and increases SOX11 protein expression, leading to increased neuronal differentiation; RBM3-SOX11 axis was identified by single-cell RNA sequencing and validated by RBM3 KD. Single-cell RNA sequencing; RBM3 KD; mRNA stability assay for SOX11; in vitro and in vivo NSC differentiation assays iScience Medium 38523796
2020 FAK/Src signaling is required for hypothermia-induced RBM3 gene transcription: FAK-specific inhibition or FAK siRNA knockdown abrogates cold-induced RBM3 expression; Src (downstream of FAK) is also required; FAK/Src inactivation abolishes the neuroprotective effects of mild hypothermia against rotenone. Signaling pathway inhibitor screen; FAK siRNA; Src siRNA/inhibitor; RT-PCR and western blot for RBM3; neuroprotection assay Biochemical and biophysical research communications Medium 33272569
2021 RBM3 overexpression increases β-catenin signaling in colorectal cancer cells by inactivating GSK3β, leading to decreased β-catenin phosphorylation, increased nuclear β-catenin, and enhanced TCF/LEF transcriptional activity, thereby inducing cancer stem cell properties. Dox-inducible RBM3 OE; β-catenin nuclear fractionation; TCF/LEF luciferase reporter; GSK3β phosphorylation; GSK3β inhibitor (BIO); side population and spheroid assays Molecular carcinogenesis Medium 26331352
2021 MZF1 is a transcription factor that directly binds the RBM3 promoter and promotes RBM3 transcription; MZF1 overexpression reduces oxidative stress and apoptosis in rotenone-treated neurons in an RBM3-dependent manner. ChIP assay; dual-luciferase reporter assay for MZF1-RBM3 promoter binding; MZF1 OE; RBM3 siRNA rescue; apoptosis and ROS assays The Journal of toxicological sciences Medium 34602532

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 217 15075239
2015 RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature 194 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
2016 Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold. Cellular and molecular life sciences : CMLS 175 27147467
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
2019 The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production. EBioMedicine 151 31235426
2008 Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene 119 18427544
2011 The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection. Neurobiology of disease 109 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 88 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 88 11470798
2019 RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury. Nature communications 77 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 71 23415676
2011 Widespread regulation of miRNA biogenesis at the Dicer step by the cold-inducible RNA-binding protein, RBM3. PloS one 67 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 66 19734850
2017 RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3. Current biology : CB 64 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 57 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
2023 Sodium butyrate induces ferroptosis in endometrial cancer cells via the RBM3/SLC7A11 axis. Apoptosis : an international journal on programmed cell death 51 37170022
2011 RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Translational oncology 51 21804916
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
2017 RNA-binding protein RBM3 prevents NO-induced apoptosis in human neuroblastoma cells by modulating p38 signaling and miR-143. Scientific reports 46 28134320
2016 RBM3 regulates temperature sensitive miR-142-5p and miR-143 (thermomiRs), which target immune genes and control fever. Nucleic acids research 46 26825461
2018 Cold-induced protein RBM3 orchestrates neurogenesis via modulating Yap mRNA stability in cold stress. The Journal of cell biology 44 30037926
2011 High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagnostic pathology 43 21955582
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 35 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 31 36946385
2019 The RNA-Binding Protein RBM3 Promotes Neural Stem Cell (NSC) Proliferation Under Hypoxia. Frontiers in cell and developmental biology 30 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 29 31566073
2019 Cold-inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling. Journal of cellular and molecular medicine 28 31436914
2021 TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection. Life science alliance 26 33563652
2020 Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome. Brain communications 26 33585816
2019 LINC00096 Promotes the Proliferation and Invasion by Sponging miR-383-5p and Regulating RBM3 Expression in Triple-Negative Breast Cancer. OncoTargets and therapy 26 31819536
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
2023 HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion. The EMBO journal 25 37248947
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
2018 Infants Uniquely Express High Levels of RBM3 and Other Cold-Adaptive Neuroprotectant Proteins in the Human Brain. Developmental neuroscience 23 30399610
2017 TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3. Scientific reports 23 28536481
2019 RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression. International journal of oncology 22 30720048
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 RBM3 expression is upregulated by NF-κB p65 activity, protecting cells from apoptosis, during mild hypothermia. Journal of cellular biochemistry 22 29388696
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
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 21 28373441
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 Stress Response Protein RBM3 Promotes the Development of Colitis-associated Cancer. Inflammatory bowel diseases 20 27930406
2017 High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer. PloS one 20 28800641
2020 Role of RBM3 in the regulation of cell proliferation in hepatocellular carcinoma. Experimental and molecular pathology 18 32976820
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.] 17 36781430
2022 RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia. Journal of cellular physiology 17 35926117
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
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
2022 RNA-binding protein RBM3 intrinsically suppresses lung innate lymphoid cell activation and inflammation partially through CysLT1R. Nature communications 14 35908044
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 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 13 36149580
2020 Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer. Cancer medicine 13 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 13 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
2024 Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway. iScience 10 38523796
2022 Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression. Apoptosis : an international journal on programmed cell death 10 35930183
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 10 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 10 33369608
2019 Prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers. Journal of cancer research and clinical oncology 10 30758670
2018 Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome. BMC cancer 10 30419865
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
2021 RBM3 Increases Cell Survival but Disrupts Tight Junction of Microvascular Endothelial Cells in Acute Lung Injury. The Journal of surgical research 9 33460967
2021 PRR11 unveiled as a top candidate biomarker within the RBM3-regulated transcriptome in pancreatic cancer. The journal of pathology. Clinical research 9 34379360
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 9 34837346
2020 Skeletal muscle RBM3 expression is associated with extended lifespan in Ames Dwarf and calorie restricted mice. Experimental gerontology 9 33385482
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
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
2023 Chronic social stress blunts core body temperature and molecular rhythms of Rbm3 and Cirbp in mouse lateral habenula. Open biology 6 37463657
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
2025 Therapeutic modulation of protein RBM3 for ischemic stroke treatment. Frontiers in pharmacology 5 40124786
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
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 5 35109796
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 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
2024 RBM3 enhances the stability of MEF2C mRNA and modulates blood-brain barrier permeability in AD microenvironment. Biochimica et biophysica acta. Molecular cell research 2 38670534
2024 Rbm3 deficiency leads to transcriptome-wide splicing alterations. RNA biology 2 39387568
2024 Cold shock proteins CIRBP and RBM3 may indicate hypothermia death: A case report. Journal of forensic and legal medicine 2 39550904

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