Affinage

RAE1

mRNA export factor RAE1 · UniProt P78406

Length
368 aa
Mass
41.0 kDa
Annotated
2026-06-10
74 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAE1 (Gle2/Mnrp41) is an evolutionarily conserved WD40 protein that folds into a seven-bladed beta-propeller and functions both at the nuclear pore complex in mRNA export and as a moonlighting regulator of mitotic spindle assembly and chromosome segregation (PMID:7706287, PMID:15851029, PMID:20498086). At the NPC, RAE1 binds directly to a GLEBS-like motif of NUP98 through its WD-repeats and a C-terminal extension, and this docking — which depends on ongoing mRNA synthesis — is required for nuclear export of poly(A)+ RNA (PMID:10209021, PMID:8970155). The 1.65 Å crystal structure shows the Nup98 GLEBS motif binding as an extended hairpin to the propeller's top face, and reveals that the Rae1–Nup98 complex acquires single-stranded RNA-binding capability through a conserved basic patch (PMID:20498086). RAE1 also bridges NUP98 to the export receptor TAP within a ternary complex, consistent with a role in delivering cargo at the pore (PMID:12637516). Independent of export, RAE1 acts as a microtubule-associated spindle assembly factor: a RanGTP/importin-β–regulated, RNA-containing RAE1 ribonucleoprotein stabilizes microtubules, RAE1 binds importin-β directly, and it interacts mitosis-specifically with NuMA to support bipolar spindle formation (PMID:15851029, PMID:17172455). RAE1, together with NUP98, restrains APC(Cdh1) by blocking ubiquitination of APC(Cdh1)-bound securin until the metaphase/anaphase transition, and RAE1 cooperates genetically with BUB3 in the mitotic checkpoint; haploinsufficiency causes premature sister-chromatid separation, aneuploidy, and embryonic lethality in mice (PMID:12551952, PMID:16355229, PMID:16479161). RAE1 abundance at the spindle is set by ubiquitination opposed by the deubiquitinase USP11 (PMID:29293652). Beyond proliferating cells, Drosophila RAE1 is a component of the Highwire/Fsn E3 ligase complex in post-mitotic neurons, where it binds and stabilizes Highwire by protecting it from autophagy (PMID:21874015). The Rae1–Nup98 RNA-binding groove is a recurrent viral target: VSV matrix protein and SARS-CoV-2 ORF6 dock through a conserved methionine-containing motif (M Met51, ORF6 Met58) that competitively displaces nucleic acid to block host mRNA export, with RAE1 also positioning ORF6 within the NPC (PMID:15629720, PMID:24927547, PMID:33849972, PMID:35096974, PMID:38507240).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Established RAE1 as an essential factor for nuclear export of poly(A)+ RNA, defining its core cellular role and its identity as a WD40-repeat protein.

    Evidence Temperature-sensitive rae1-1 mutant analysis with FISH for poly(A)+ RNA and complementation cloning in S. pombe

    PMID:7706287

    Open questions at the time
    • Molecular partners at the pore not yet identified
    • Cytoskeletal and cell-cycle phenotypes left mechanistically unexplained
  2. 1996 High

    Localized the ortholog (Gle2) physically to nuclear pore complexes and showed its loss perturbs NPC/nuclear envelope architecture, tying export function to the pore itself.

    Evidence Immunofluorescence, NPC fractionation, EM and genetic screening in S. cerevisiae

    PMID:8970155

    Open questions at the time
    • Direct NPC anchoring partner not defined
    • Mechanism of structural perturbation unresolved
  3. 1997 Medium

    Demonstrated functional conservation to human RAE1 and separated its mitotic role from mRNA export in yeast, hinting at a moonlighting function.

    Evidence Cross-species complementation in S. pombe and Cdc2p kinase/cell-cycle analysis

    PMID:9301023 PMID:9370289

    Open questions at the time
    • Partial suppression only
    • Mitotic mechanism unknown at this stage
  4. 1999 High

    Identified NUP98 as the direct NPC-docking partner via a GLEBS-like motif and tied RAE1 docking to active mRNA synthesis, providing the molecular basis for export function.

    Evidence In vitro binding, cross-linking and Xenopus oocyte microinjection with dominant-negative GLEBS overexpression

    PMID:10209021

    Open questions at the time
    • Structural basis of binding not yet resolved
    • How RNA cargo is engaged unclear
  5. 2003 High

    Resolved RAE1's in vivo function as a mitotic checkpoint factor cooperating with BUB3, showing chromosome-segregation roles can be genetically separated from mRNA export.

    Evidence Knockout/haploinsufficient mouse genetics with cytogenetics, checkpoint assays and mRNA export assays

    PMID:12551952

    Open questions at the time
    • Biochemical mechanism linking RAE1 to checkpoint not defined
    • Relationship between BUB3 and NUP98 roles unclear
  6. 2003 Medium

    Placed RAE1 in a NUP98–TAP ternary complex, suggesting it functions as an adaptor that hands export cargo/receptor to NUP98.

    Evidence In vitro binary/ternary complex reconstitution with competition pull-downs

    PMID:12637516

    Open questions at the time
    • Delivery model not directly demonstrated in cells
    • Single lab in vitro evidence
  7. 2005 High

    Defined the dual mitotic mechanisms: RAE1 as a RanGTP/importin-β–regulated, RNA-dependent microtubule-stabilizing RNP, and as an APC(Cdh1) inhibitor protecting securin from premature ubiquitination.

    Evidence Xenopus egg extract purification, immunodepletion, in vitro microtubule and ubiquitination assays, and haploinsufficient mouse genetics

    PMID:15851029 PMID:16355229

    Open questions at the time
    • Identity of the RNA in the spindle RNP unknown
    • How RAE1 senses the metaphase/anaphase transition unresolved
  8. 2005 High

    Revealed RAE1 as a direct viral target, with VSV M protein binding it to block host mRNA export, establishing RAE1 as a host-pathogen interface.

    Evidence Co-immunoprecipitation, M-protein binding mutant and Rae1 overexpression rescue of export

    PMID:15629720

    Open questions at the time
    • Structural basis of M–RAE1 interaction not yet defined
    • Whether NUP98 participates not established here
  9. 2006 High

    Refined the securin-protection mechanism and identified NuMA as the mitotic spindle partner mediating bipolar spindle assembly.

    Evidence Co-IP, domain mapping and reciprocal knockdown/overexpression rescue in HeLa cells; cell-cycle timing analyses

    PMID:16479161 PMID:17172455

    Open questions at the time
    • How RAE1–NuMA binding is regulated within the cycle unclear
    • Securin-priming model rests on co-IP interpretation
  10. 2010 High

    Provided atomic resolution of the RAE1 beta-propeller bound to the Nup98 GLEBS hairpin and demonstrated the complex's intrinsic single-stranded RNA-binding via a basic patch, unifying the structural and functional pictures.

    Evidence 1.65 Å X-ray crystallography with GLEBS mutagenesis and in vitro RNA-binding assay

    PMID:20498086

    Open questions at the time
    • Sequence specificity of RNA binding not defined
    • Link between this RNA groove and spindle RNP unestablished
  11. 2011 High

    Extended RAE1 function into post-mitotic neurons as a Highwire E3-ligase component that stabilizes Highwire against autophagy, a role distinct from export and mitosis.

    Evidence Tandem affinity purification, co-IP, genetic epistasis and autophagy-inhibitor experiments in Drosophila

    PMID:21874015

    Open questions at the time
    • Whether this neuronal role is conserved in mammals untested in corpus
    • Mechanism of autophagy protection unresolved
  12. 2011 Medium

    Showed NUP98 controls RAE1 expression and localization and that the complex governs chromosome segregation, with disruption in NUP98-HOXA9 leukemia.

    Evidence RNAi, rescue, IF localization and chromosome segregation assays with transgenic mouse and patient samples

    PMID:21467841

    Open questions at the time
    • Direct contribution to leukemogenesis not isolated
    • Single lab
  13. 2014 High

    Defined the structural mechanism of viral hijacking: VSV M Met51 inserts into a hydrophobic pocket and competes with nucleic acid for the RAE1–Nup98 groove, establishing ligand mimicry.

    Evidence 3.15 Å crystal structure with in vitro nucleic acid competition and synthetic peptide assays

    PMID:24927547

    Open questions at the time
    • Physiological RNA ligand of the groove still undefined
    • Mechanism extrapolated to other viruses not yet tested here
  14. 2018 Medium

    Identified USP11 as the deubiquitinase setting RAE1 levels at the spindle and modulating its NuMA interaction, adding post-translational control of the mitotic function.

    Evidence Lentiviral knockdown, co-IP, ubiquitination assay and spindle morphology analysis

    PMID:29293652

    Open questions at the time
    • E3 ligase opposing USP11 on RAE1 not identified
    • Single lab
  15. 2023 Medium

    Connected the RAE1–NUP98 complex to a nucleoplasmic, chromatin-associated role controlling epidermal progenitor proliferation versus differentiation via epigenetic regulator loci.

    Evidence siRNA knockdown, ChIP, fractionation and HDAC-inhibitor relocalization assays

    PMID:37353594

    Open questions at the time
    • Direct RAE1 chromatin contacts vs. NUP98-mediated not separated
    • Single lab
  16. 2024 High

    Showed SARS-CoV-2 ORF6 hijacks the same RAE1–Nup98 groove (ORF6 Met58) to block transport and that RAE1 is required to position ORF6 within the NPC, completing the viral-mimicry paradigm across two virus families.

    Evidence Co-IP, Met58 mutagenesis, reporter and transport assays, crystallography of ORF6–Rae1–Nup98, and siRNA/SARS-CoV-2 infection assays

    PMID:33849972 PMID:35096974 PMID:38507240

    Open questions at the time
    • Endogenous transport function of RAE1 partly dispensable under normal conditions, raising redundancy questions
    • Why RAE1 loss broadly disables ORF6 not fully mechanistically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous RNA ligand bound by the RAE1–Nup98 groove and the RNA species in the mitotic spindle RNP remain unidentified, leaving the link between RAE1's export and spindle functions unresolved.
  • No physiological RNA cargo defined
  • Mechanistic unification of NPC versus spindle roles incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-9609507 Protein localization 2
Partners
BUB3HIGHWIREIMPORTIN-BETANUMANUP98SECURINTAPUSP11
Complex memberships
APC(Cdh1)-Rae1-Nup98-securin complexHighwire/Fsn E3 ubiquitin ligase complexRae1-Nup98 complexRae1-Nup98-TAP ternary complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 S. pombe Rae1 is required for nuclear export of poly(A)+ RNA; temperature-sensitive rae1-1 mutant accumulates poly(A)+ RNA in the nucleus within 30 min at restrictive temperature. Rae1 encodes a WD40-repeat protein, and loss of function also causes actin/tubulin disorganization and irreversible cell cycle arrest, with cells being particularly vulnerable during G2/M. Fluorescence in situ hybridization (FISH) to detect poly(A)+ RNA localization; complementation cloning; temperature-shift experiments The Journal of biological chemistry High 7706287
1996 S. cerevisiae Gle2 (ortholog of RAE1) associates with nuclear pore complexes and is required for poly(A)+ RNA export but not nuclear protein import; gle2 mutants show severe NPC and nuclear envelope structural perturbations. Two-hybrid interactions with Srp1p (NLS receptor) and Rip1p (NES-interacting protein) were detected. Indirect immunofluorescence; NPC fractionation; colony-sectoring genetic screen; thin-section electron microscopy; two-hybrid assay Molecular biology of the cell High 8970155
1997 Human RAE1 is a functional homolog of S. pombe rae1; human RAE1 cDNA partially suppresses the temperature-sensitivity and poly(A)+ RNA export defect of the rae1-1 mutant. Epitope-tagged human Rae1 localizes to both nucleus and cytoplasm in HeLa cells. Cross-species complementation in S. pombe; FISH for poly(A)+ RNA; immunofluorescence in HeLa cells Gene Medium 9370289
1997 S. pombe Rae1 is required for cell cycle progression through mitosis independent of mRNA export; rae1-loss cells arrest with elevated Cdc2p kinase before spindle formation and without spindle pole body separation. Rae1p localizes to the nuclear periphery. Temperature-shift cell cycle analysis; Cdc2p kinase assay; immunofluorescence localization Yeast Medium 9301023
1999 Mammalian RAE1 binds directly to a GLEBS-like motif within NUP98 at the nuclear pore complex through multiple domains including WD-repeats and a C-terminal non-WD extension. RAE1 shuttles between nucleus and cytoplasm in a temperature-dependent, RanGTP-independent manner. NE docking of RAE1 requires new mRNA synthesis. Overexpression of the GLEBS-like motif inhibits NE binding of RAE1 and induces nuclear poly(A)+ RNA accumulation, effects reversed by RAE1 overexpression. In vitro binding studies; chemical cross-linking; microinjection in Xenopus oocytes; overexpression/dominant-negative experiments; FISH for poly(A)+ RNA The Journal of cell biology High 10209021
2000 Ct-RAE1 (Chironomus tentans ortholog) does not associate with mRNPs co-transcriptionally or in the nucleoplasm; instead, it interacts with exported BR RNP particles specifically at the nuclear pore complex. RAE1 is not found on the cytoplasmic side of the RNP in transit, suggesting it remains anchored at the nuclear face of the NPC or is rapidly released. Immunoelectron microscopy on Balbiani ring RNP particles RNA Medium 11105759
2003 Mammalian Rae1 haploinsufficiency causes mitotic checkpoint defects and chromosome missegregation in vivo; Rae1-null mice are embryonic lethal. Overexpression of Rae1 can rescue both Rae1 and Bub3 haploinsufficiency. Combined Rae1/Bub3 haploinsufficiency greatly amplifies premature sister chromatid separation. Rae1 and Bub3 have essential, overlapping roles in the mitotic checkpoint. Cells from Rae1/Bub3-null mice show no detectable defect in mRNA nuclear export. Knockout mouse generation; cytogenetic analysis; spindle checkpoint assays; mRNA export assays; overexpression rescue experiments The Journal of cell biology High 12551952
2003 Rae1, Nup98, and TAP form a ternary complex at the nuclear pore. Gle2/Rae1 requires two sites within TAP for stable interaction. TAP has highest affinity for a specific region within the GLFG domain of Nup98. When Rae1 is bound to Nup98, it no longer interacts directly with TAP, suggesting a mechanism where Rae1 may deliver TAP to Nup98. In vitro binding assays; definition of binary and ternary complexes by pull-down and competition experiments The Journal of biological chemistry Medium 12637516
2005 VSV matrix (M) protein inhibits host mRNA nuclear export by binding the mRNA export factor Rae1/mrnp41. A M protein mutant defective in Rae1 binding cannot inhibit mRNA export. Overexpression of Rae1 fully reverses M protein-mediated inhibition of mRNA export. Rae1 is induced by interferon-gamma. Co-immunoprecipitation; dominant-negative M protein mutant; mRNA export assay; overexpression rescue; IFN-gamma treatment Molecular cell High 15629720
2005 Rae1 is a microtubule-associated protein and spindle assembly factor regulated by the RanGTP/importin-beta pathway. Rae1 binds directly to importin beta. Depletion of Rae1 from Xenopus egg extracts or cells severely inhibits mitotic spindle assembly. A purified Rae1-containing ribonucleoprotein complex stabilizes microtubules in a RanGTP/importin beta-regulated manner, and this activity requires RNA. Activity-based biochemical purification from Xenopus egg extracts; immunodepletion; in vitro microtubule stabilization assay; direct binding assay with importin beta Cell High 15851029
2005 Rae1 and Nup98 form a complex with Cdh1-activated APC (APC(Cdh1)) in early mitosis and specifically inhibit APC(Cdh1)-mediated ubiquitination of securin, preventing premature securin degradation until the metaphase/anaphase transition. Combined Rae1/Nup98 haploinsufficiency in mice results in premature sister chromatid separation, severe aneuploidy, and untimely securin degradation. Co-immunoprecipitation of APC(Cdh1) complex; ubiquitination assay; haploinsufficient mouse genetics; cytogenetic analysis; securin degradation timing assay Nature High 16355229
2006 The Rae1-Nup98 complex also forms a complex with securin in prometaphase. This complex does not prevent APC(Cdh1) from binding securin, but instead prevents ubiquitination of APC(Cdh1)-bound securin, priming rapid securin degradation after dissociation of Rae1-Nup98 at the metaphase/anaphase transition. Co-immunoprecipitation; cell cycle timing analysis; genetic mouse models Cell cycle Medium 16479161
2006 Rae1 interacts with the nuclear mitotic apparatus protein NuMA in a mitosis-specific manner. A specific binding site for Rae1 on NuMA was mapped. This interaction is required for bipolar spindle formation; reducing Rae1 or increasing NuMA causes spindle abnormalities. Coupling NuMA overexpression with Rae1 overexpression, or depleting both simultaneously, prevents aberrant spindle formation. Overexpression of the Rae1-binding domain of NuMA in HeLa cells causes aberrant spindles. Co-immunoprecipitation; domain mapping; siRNA knockdown and overexpression in HeLa cells; spindle morphology analysis Proceedings of the National Academy of Sciences of the United States of America High 17172455
2008 Retinoic acid downregulates Rae1 expression in human SH-SY5Y neuroblastoma cells, thereby facilitating APC(Cdh1)-mediated Skp2 degradation, p27 stabilization, and neuroblastoma differentiation. Rae1 overexpression promotes Skp2 accumulation and prevents retinoic acid-induced cell cycle arrest; Rae1 inhibition accelerates differentiation. Western blotting; siRNA knockdown; overexpression; cell cycle analysis; measurement of Skp2 and p27 levels Oncogene Medium 18212744
2010 Crystal structure of human Rae1 in complex with the Nup98 GLEBS motif determined at 1.65 Å resolution. Rae1 forms a seven-bladed beta-propeller. The Nup98 GLEBS motif forms an ~50 Å-long hairpin binding to an invariant hydrophobic surface on the top face of Rae1. The C-terminal arm of the GLEBS hairpin is necessary and sufficient for Rae1 binding; a tandem glutamate element in this arm is critical. The Rae1-Nup98 complex possesses single-stranded RNA-binding capability via a conserved basic patch. X-ray crystallography at 1.65 Å; mutagenesis of GLEBS motif; in vitro RNA-binding assay Proceedings of the National Academy of Sciences of the United States of America High 20498086
2011 RNAi knockdown of NUP98 in human cells disrupts RAE1 expression and localization (but not HDAC1). Rescue experiments show that the RAE1-NUP98 complex orchestrates proper chromosome segregation. In NUP98-HOXA9-transfected cells, RAE1 protein is reduced and mis-localized. This is confirmed in NUP98-HOXA9 transgenic mice and AML patient samples. RNAi knockdown; rescue experiments; immunofluorescence localization; chromosome segregation assays; transgenic mouse analysis; patient sample analysis Cell cycle Medium 21467841
2011 Drosophila Rae1 is a component of the Highwire (Hiw)/Fsn E3 ubiquitin ligase complex in post-mitotic neurons. Rae1 physically and genetically interacts with Hiw. Loss of Rae1 in neurons produces NMJ morphological defects similar to hiw mutants. Rae1 is necessary and sufficient to promote Hiw protein abundance by binding Hiw and protecting it from autophagy-mediated degradation. Tandem affinity purification; co-immunoprecipitation; genetic epistasis; loss-of-function neuronal phenotype analysis; autophagy inhibitor experiments Nature neuroscience High 21874015
2012 VSV M protein forms multiple distinct complexes with Rae1 and Nup98 (high, intermediate, and low molecular weight). The intermediate MW complexes containing Nup98 interact most efficiently with M protein. Silencing Rae1 reduces VSV's ability to inhibit host transcription but does not affect nuclear mRNA accumulation or inhibition of translation. M protein-Rae1-Nup98 complexes associate with the chromatin fraction, suggesting a role in inhibiting host transcription. Size exclusion chromatography; sedimentation velocity analysis; siRNA silencing; mRNA export assay; translation assay; chromatin fractionation PLoS pathogens Medium 23028327
2013 Drosophila Rae1 localizes to the nuclear envelope and is required for normal male meiosis: rae1 mutants display defects in primary spermatocyte nuclear integrity, meiotic chromosome condensation, segregation, and spindle morphology, leading to failure to complete meiosis. GFP-RAE1 dynamically localizes to the nuclear envelope, chromatin, and other structures during spermatogenesis. Genetic mutant analysis; immunofluorescence; GFP-RAE1 live imaging; RNAi Journal of cell science Medium 23788425
2014 Crystal structure of VSV M protein in complex with Rae1 and Nup98 at 3.15 Å resolution. M protein contacts the Rae1-Nup98 heterodimer via two protrusions (finger and thumb). The conserved Met51 of M inserts into a deep hydrophobic pocket on the Rae1 beta-propeller; flanking acidic residues bond to a basic groove on Rae1. M protein competes with oligonucleotides for binding to Rae1-Nup98 in vitro. A synthetic peptide corresponding to the finger competes for nucleic acid binding, suggesting Rae1 binds the phosphate backbone of any nucleic acid and M mimics this ligand. X-ray crystallography at 3.15 Å; in vitro nucleic acid competition binding assay; synthetic peptide competition Proceedings of the National Academy of Sciences of the United States of America High 24927547
2016 The Hippo pathway targets Rae1 for degradation downstream of Warts/Lats. In proliferating cells, Rae1 loss restricts cyclin B levels and organ size; Rae1 overexpression increases cyclin B and organ size. Reducing Rae1 blocks cyclin B accumulation and suppresses overgrowth caused by Hippo pathway loss. Rae1 also acts in a feedback circuit to increase protein levels of Merlin, Hippo, and Warts and to reduce Yki/YAP levels. Genetic epistasis in Drosophila tissues and cells; biochemical studies; mammalian cell overexpression/knockdown; cyclin B and organ size measurements PLoS genetics Medium 27494403
2018 USP11 is a deubiquitinating enzyme for RAE1; USP11 controls RAE1 ubiquitination at the mitotic spindle. USP11 localizes to the mitotic spindle and its knockdown (or RAE1 knockdown) reduces cell proliferation and increases multipolar spindle formation. USP11 does not regulate spindle assembly checkpoint inactivation but modulates RAE1's interaction with NuMA. Lentiviral knockdown; co-immunoprecipitation; ubiquitination assay; spindle morphology analysis; localization by immunofluorescence PloS one Medium 29293652
2019 RAE1 directly binds to the promoter region of the EMT transcription factor ZEB1 in breast cancer cells, mediating its upregulation. RAE1 overexpression induces EMT and invasive/migratory behavior; ZEB1 knockdown in RAE1-overexpressing cells suppresses invasiveness and restores epithelial markers. ChIP (promoter binding assay); siRNA knockdown of ZEB1 in RAE1-overexpressing cells; 3D culture; xenograft models; invasion/migration assays Scientific reports Medium 30814639
2021 SARS-CoV-2 ORF6 blocks nuclear mRNA export and inhibits nuclear import of host proteins by co-purifying with Rae1 and Nup98. Interactions map to the C terminus of ORF6 and a single mutation at Met58 abolishes binding. Overexpression of Rae1 restores reporter expression suppressed by ORF6. SARS-CoV-2 ORF6 more strongly copurifies with Rae1 and Nup98 than SARS-CoV ORF6. Co-immunoprecipitation; site-directed mutagenesis (Met58); reporter assay; nuclear mRNA accumulation assay; overexpression rescue mBio High 33849972
2022 Crystal structures of both SARS-CoV-2 and SARS-CoV-1 ORF6 C-termini in complex with the Rae1-Nup98 heterodimer were determined. ORF6 occupies the same potential mRNA-binding groove of the Rae1-Nup98 complex as VSV M protein. The conserved Met58 of ORF6 is critical for complex formation and competitive inhibition of RNA binding to Rae1-Nup98. X-ray crystallography; biochemical binding assays; site-directed mutagenesis; RNA competition binding assay Frontiers in molecular biosciences High 35096974
2023 NUP98 and RAE1 are highly expressed in epidermal progenitors and form a distinct nucleoplasmic complex. Reduction of NUP98 or RAE1 abolishes progenitor regenerative capacity, inhibiting proliferation and inducing premature terminal differentiation. NUP98 binds chromatin near transcription start sites of key epigenetic regulators (DNMT1, UHRF1, EZH2) co-occupied by HDAC1. HDAC inhibition diminishes NUP98 chromatin binding and induces NUP98 and RAE1 to relocalize interdependently to the nucleolus. siRNA knockdown; ChIP; immunofluorescence fractionation; HDAC inhibitor treatment; proliferation and differentiation assays Communications biology Medium 37353594
2024 Rae1 is required to position SARS-CoV-2 ORF6 within the NPC to inhibit nucleocytoplasmic transport. Loss of Rae1 suppresses ORF6's transport inhibitory activity. Rae1 alone is not necessary for p-STAT1 import or poly(A) RNA export under normal conditions. Rae1 is also required for normal viral protein production during SARS-CoV-2 infection, presumably through supporting ORF6 function. siRNA knockdown of Rae1; nuclear transport assays (p-STAT1 import, poly(A) RNA export); SARS-CoV-2 infection; viral protein production assay Molecular biology of the cell Medium 38507240
2023 RAE1 regulates PPARα mRNA stability in esophageal epithelial cells; RAE1 knockdown causes G2/M cell cycle blockade and reduced lipid accumulation, phenocopied by PPARα downregulation. RAE1 overexpression promotes malignant transformation by maintaining PPARα mRNA stability. siRNA knockdown; overexpression; mRNA stability assay; cell cycle analysis; xenograft tumor model Ecotoxicology and environmental safety Low 37774541

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 756 11557981
2001 Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proceedings of the National Academy of Sciences of the United States of America 454 11562472
2001 Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics 377 11491531
2003 Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. The Journal of cell biology 302 12551952
2005 A Rae1-containing ribonucleoprotein complex is required for mitotic spindle assembly. Cell 232 15851029
1999 RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at the nuclear pore complex through multiple domains. The Journal of cell biology 209 10209021
2005 VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway. Molecular cell 200 15629720
2005 The Rae1-Nup98 complex prevents aneuploidy by inhibiting securin degradation. Nature 157 16355229
2014 RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma. Cancer research 149 24590060
1996 GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function. Molecular biology of the cell 149 8970155
2006 Early aging-associated phenotypes in Bub3/Rae1 haploinsufficient mice. The Journal of cell biology 148 16476774
1995 A mutation in the Schizosaccharomyces pombe rae1 gene causes defects in poly(A)+ RNA export and in the cytoskeleton. The Journal of biological chemistry 142 7706287
2008 Mononuclear myeloid-derived "suppressor" cells express RAE-1 and activate natural killer cells. Blood 128 18753637
2021 SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through Interactions with Rae1 and Nup98. mBio 126 33849972
2003 Complex formation among the RNA export proteins Nup98, Rae1/Gle2, and TAP. The Journal of biological chemistry 113 12637516
2010 Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1. Proceedings of the National Academy of Sciences of the United States of America 101 20498086
2007 Retinoic acid signaling sensitizes hepatic stellate cells to NK cell killing via upregulation of NK cell activating ligand RAE1. American journal of physiology. Gastrointestinal and liver physiology 101 17673545
2012 RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry. The Journal of experimental medicine 100 23166357
2006 Rae1 interaction with NuMA is required for bipolar spindle formation. Proceedings of the National Academy of Sciences of the United States of America 96 17172455
2014 IL-30 (IL27p28) attenuates liver fibrosis through inducing NKG2D-rae1 interaction between NKT and activated hepatic stellate cells in mice. Hepatology (Baltimore, Md.) 89 25351459
1996 Genomic structures and characterization of Rae1 family members encoding GPI-anchored cell surface proteins and expressed predominantly in embryonic mouse brain. Journal of biochemistry 85 8982867
2001 Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60. Immunity 83 11520456
2012 Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription. PLoS pathogens 67 23028327
2020 Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex. Biochemical and biophysical research communications 63 33360543
2014 Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1 • Nup98). Proceedings of the National Academy of Sciences of the United States of America 61 24927547
2008 Retinoic acid downregulates Rae1 leading to APC(Cdh1) activation and neuroblastoma SH-SY5Y differentiation. Oncogene 56 18212744
1997 The human RAE1 gene is a functional homologue of Schizosaccharomyces pombe rae1 gene involved in nuclear export of Poly(A)+ RNA. Gene 53 9370289
2006 Securin associates with APCCdh1 in prometaphase but its destruction is delayed by Rae1 and Nup98 until the metaphase/anaphase transition. Cell cycle (Georgetown, Tex.) 51 16479161
2011 Expression of the RAE-1 family of stimulatory NK-cell ligands requires activation of the PI3K pathway during viral infection and transformation. PLoS pathogens 46 21966273
2003 Natural killer cell-mediated lysis of dorsal root ganglia neurons via RAE1/NKG2D interactions. European journal of immunology 46 12594837
2009 Dual functions of Nicotiana benthamiana Rae1 in interphase and mitosis. The Plant journal : for cell and molecular biology 45 19392703
2011 RNA export factor RAE1 contributes to NUP98-HOXA9-mediated leukemogenesis. Cell cycle (Georgetown, Tex.) 42 21467841
2011 Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in post-mitotic neurons. Nature neuroscience 42 21874015
2022 Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1-Nup98 Complex to Compete With mRNA Nuclear Export. Frontiers in molecular biosciences 41 35096974
2012 RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 22357847
2010 Intact NKG2D-independent function of NK cells chronically stimulated with the NKG2D ligand Rae-1. Journal of immunology (Baltimore, Md. : 1950) 36 20530257
2009 Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus. Journal of virology 36 19494006
1997 Advancement through mitosis requires rae1 gene function in fission yeast. Yeast (Chichester, England) 36 9301023
2006 The effect of renal ischemia-reperfusion injury on expression of RAE-1 and H60 in mice kidney. Transplantation proceedings 29 16980040
2017 Rae1/YacP, a new endoribonuclease involved in ribosome-dependent mRNA decay in Bacillus subtilis. The EMBO journal 27 28363943
2013 Drosophila rae1 is required for male meiosis and spermatogenesis. Journal of cell science 26 23788425
2010 Direct interaction of the mouse cytomegalovirus m152/gp40 immunoevasin with RAE-1 isoforms. Biochemistry 26 20166740
2021 Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer. Cancer science 25 34008277
2011 RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres. Glia 23 21046555
2004 Characterization of the Drosophila Rae1 protein as a G1 phase regulator of the cell cycle. Gene 22 14729268
2016 A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression. eLife 21 27874833
2018 USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation. PloS one 20 29293652
2002 High levels of RAE-1 isoforms on mouse tumor cell lines assessed by anti-"pan" RAE-1 antibody confer tumor susceptibility to NK cells. Biochemical and biophysical research communications 19 11779145
2019 RAE1 mediated ZEB1 expression promotes epithelial-mesenchymal transition in breast cancer. Scientific reports 16 30814639
2000 The Ct-RAE1 protein interacts with Balbiani ring RNP particles at the nuclear pore. RNA (New York, N.Y.) 16 11105759
2016 RAE-1 expression is induced during experimental autoimmune encephalomyelitis and is correlated with microglia cell proliferation. Brain, behavior, and immunity 15 27444966
2017 The mitotic checkpoint regulator RAE1 induces aggressive breast cancer cell phenotypes by mediating epithelial-mesenchymal transition. Scientific reports 14 28181567
2016 The Hippo Pathway Targets Rae1 to Regulate Mitosis and Organ Size and to Feed Back to Regulate Upstream Components Merlin, Hippo, and Warts. PLoS genetics 12 27494403
2020 Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model. Medical science monitor : international medical journal of experimental and clinical research 11 32599603
2024 SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to inhibit nucleocytoplasmic transport. Molecular biology of the cell 10 38507240
2017 Activity analysis of LTR12C as an effective regulatory element of the RAE1 gene. Gene 10 28867566
2013 Activation of cellular immunity and marked inhibition of liver cancer in a mouse model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1. Molecular cancer 10 24350772
2012 Polymeric delivery of therapeutic RAE-1 plasmid to the pancreatic islets for the prevention of type 1 diabetes. Journal of controlled release : official journal of the Controlled Release Society 10 22910142
2023 NUP98 and RAE1 sustain progenitor function through HDAC-dependent chromatin targeting to escape from nucleolar localization. Communications biology 9 37353594
2020 Lysine acetylation of NKG2D ligand Rae-1 stabilizes the protein and sensitizes tumor cells to NKG2D immune surveillance. Cancer letters 9 33279621
2017 Rae1-mediated nuclear export of Rnc1 is an important determinant in controlling MAPK signaling. Current genetics 9 28799069
2014 Generation of a monoclonal antibody against the glycosylphosphatidylinositol-linked protein Rae-1 using genetically engineered tumor cells. Biological procedures online 8 24495546
2020 Rae1 drives NKG2D binding-dependent tumor development in mice by activating mTOR and STAT3 pathways in tumor cells. Cancer science 7 32333709
2023 Shutdown of multidrug transporter bmrCD mRNA expression mediated by the ribosome-associated endoribonuclease (Rae1) cleavage in a new cryptic ORF. RNA (New York, N.Y.) 5 37142436
2023 RAE1 promotes nitrosamine-induced malignant transformation of human esophageal epithelial cells through PPARα-mediated lipid metabolism. Ecotoxicology and environmental safety 5 37774541
2025 The Chlamydia trachomatis secreted effector CebN targets nucleoporins and Rae1 to antagonize STAT1 nuclear import. bioRxiv : the preprint server for biology 4 38712050
2006 Yisheng injection decreases the expression of H60 and RAE-1 genes in ischemic mice liver. Transplantation proceedings 4 16980045
2024 RAE1 promotes gastric carcinogenesis and epithelial-mesenchymal transition. Archives of biochemistry and biophysics 3 38417691
2017 Saccharomyces cerevisiae Gle2/Rae1 is involved in septin organization, essential for cell cycle progression. Yeast (Chichester, England) 3 28776765
2025 RAE1-armoured DC vaccine boosts NKG2D-CAR-T cells elicited anti-solid tumour treatment. Pharmacological research 2 40683483
2024 Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism. Cancer science 2 39526400
2025 Nuclearporin subcomplex Nup98/Rae1 is vital for maternal-to-zygotic transition during early embryonic development. Theriogenology 0 40483744
2007 [Effects of NKG2D and its ligands RAE-1 and H60 on graft-versus-tumor response]. Zhongguo shi yan xue ye xue za zhi 0 17490545
2002 [Establishment of rat alveolar type II epithelial cell line RAE-1 and its biological characteristics]. Wei sheng yan jiu = Journal of hygiene research 0 12545745

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