Affinage

GLE1

mRNA export factor GLE1 · UniProt Q53GS7

Length
698 aa
Mass
79.8 kDa
Annotated
2026-04-28
49 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLE1 is a conserved regulator of DEAD-box RNA helicases that couples nuclear pore complex (NPC) function to mRNA export, translation, and transcription termination. At the cytoplasmic face of the NPC, where it is anchored via interactions with Nup155, hCG1, and Nup42, IP6-bound Gle1 activates Dbp5/DDX19B by thermodynamically coupling its own binding to ATP loading on Dbp5 (>150-fold increase in ATP affinity) and accelerating rate-limiting phosphate release ~20-fold, driving iterative mRNP remodeling for directional mRNA and tRNA export (PMID:16783363, PMID:35286399, PMID:38189406). Gle1 also inhibits the DEAD-box helicase Ded1/DDX3 in an IP6-independent manner to modulate translation initiation, interacts with eIF3 and translation termination factors for broader translational control, and coordinates DDX1 function in nuclear transcription termination and 3′-end processing (PMID:21949122, PMID:18724935, PMID:32755435). Gle1 oligomerization via its coiled-coil domain is specifically required for mRNA export and stress granule dynamics—the latter regulated by MAPK/GSK3-mediated phosphorylation—and disease-causing mutations in LCCS1/LAAHD disrupt oligomer architecture and NPC localization (PMID:24243016, PMID:30429220).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Establishing that hGle1 localizes to the NPC via Nup155 binding and shuttles between nucleus and cytoplasm answered how Gle1 is positioned to function in mRNA export.

    Evidence FRAP, microinjection, cell-permeable peptide competition in HeLa cells; yeast two-hybrid and in vitro pulldowns for Nup155 interaction

    PMID:12668658 PMID:14645504

    Open questions at the time
    • Structural basis of Gle1-Nup155 interface not resolved
    • Whether shuttling is cargo-associated or autonomous was unclear
  2. 2005 High

    Identification of the hGle1B–hCG1–Nup155 heterotrimeric complex at the NPC cytoplasmic face defined the molecular platform through which Gle1 is tethered for mRNA export.

    Evidence In vitro reconstitution of trimeric complex, siRNA depletion of hCG1 with mRNA export readout

    PMID:16000379

    Open questions at the time
    • Stoichiometry of the complex at the intact NPC not determined
    • Contribution of Nup42 to human NPC tethering not yet tested
  3. 2006 High

    Demonstrating that Gle1 and IP6 together stimulate Dbp5 ATPase activity revealed the enzymatic mechanism by which Gle1 drives directional mRNA export at the NPC.

    Evidence In vitro ATPase kinetic assays and genetic epistasis, independently replicated by two labs

    PMID:16783363 PMID:16783364

    Open questions at the time
    • Precise kinetic mechanism of stimulation (binding vs. catalysis) not yet dissected
    • Whether Gle1-IP6 activates other DEAD-box proteins was unknown
  4. 2008 High

    Discovery that Gle1 functions in both translation termination (IP6-dependent, with termination factors) and translation initiation (via eIF3, IP6-independent) expanded Gle1's role beyond mRNA export to cytoplasmic gene expression control.

    Evidence Co-immunoprecipitation with termination factors and eIF3, genetic interactions with nip1-1, in vivo translation assays in S. cerevisiae

    PMID:18724935

    Open questions at the time
    • Direct target helicase for translation termination role not identified
    • Mechanism of eIF3 interaction not structurally resolved
  5. 2009 High

    Crystal structure of Dbp5 C-terminal domain mapped the Gle1-interaction surface and showed that charge-complementary residues are essential for Gle1-stimulated ATPase activity and viability.

    Evidence X-ray crystallography at 1.8 Å, structure-guided mutagenesis with in vitro and in vivo validation

    PMID:19805289

    Open questions at the time
    • Full Gle1-Dbp5 co-crystal structure not obtained
    • Conformational changes upon Gle1 binding not visualized
  6. 2010 High

    Mapping the IP6 binding pocket on Gle1 and showing that IP6-binding mutants phenocopy IP6-depleted cells established Gle1 as the primary effector of IP6 signaling in both mRNA export and translation termination.

    Evidence Structure-guided Gle1 point mutants tested in vitro (ATPase stimulation) and in vivo (export and translation assays)

    PMID:20371601

    Open questions at the time
    • Whether IP6 binding induces a conformational change in Gle1 was not determined
  7. 2011 High

    Reconstitution of the Dbp5 catalytic cycle showed that Gle1-IP6 stimulates ATP binding and primes RNA loading while Nup159 modulates nucleotide state, explaining how a single Dbp5 molecule performs multiple remodeling cycles at the NPC.

    Evidence In vitro ATPase reconstitution, Dbp5 mutant bypass analysis, FRAP dynamics, dominant-negative competition

    PMID:21576265 PMID:21576266

    Open questions at the time
    • Precise role of Nup159 in ADP release versus Gle1 dissociation debated
    • Real-time single-molecule visualization of the cycle not achieved
  8. 2011 High

    Finding that Gle1 inhibits Ded1 ATPase activity (IP6-independently) revealed that Gle1 can both activate and inhibit distinct DEAD-box helicases, with opposing effects tuning translation initiation.

    Evidence In vitro ATPase inhibition assays, co-IP, genetic suppression of ded1-120 by gle1-4, in vitro translation

    PMID:21949122

    Open questions at the time
    • Structural basis for differential activation (Dbp5) versus inhibition (Ded1) unknown
    • Whether inhibition occurs on polysomes or free mRNPs not resolved
  9. 2013 High

    Demonstration that Gle1 forms disk-shaped oligomers via its coiled-coil domain and that the LCCS1 FinMajor mutation disrupts oligomerization and specifically impairs mRNA export (but not translation) linked a human disease mechanism to a discrete structural feature of Gle1.

    Evidence Electron microscopy of oligomeric particles, in vitro self-association assays, in vivo dissection of export versus translation in FinMajor mutants

    PMID:24243016

    Open questions at the time
    • Oligomer stoichiometry and arrangement within the NPC not resolved
    • Whether other LAAHD/ALS mutations also disrupt oligomerization not systematically tested
  10. 2017 High

    Reconstitution of the Nup42-Gle1-Dbp5 trimeric complex and demonstration that Nup42 and IP6 non-additively enhance Gle1-mediated Dbp5 activation clarified how NPC-tethered Gle1 achieves maximal helicase stimulation in situ.

    Evidence In vitro trimeric complex reconstitution, ATPase stimulation, structure-function mutagenesis in yeast and human cells

    PMID:28869701

    Open questions at the time
    • Cryo-EM or crystal structure of the intact trimeric complex not obtained
  11. 2017 Medium

    Showing that Gle1 inhibits Ded1 by reducing its RNA affinity defined the molecular mechanism through which Gle1 gates Ded1-mediated translation repression.

    Evidence RNA binding assays with Ded1 mutants, in vitro translation, genetic suppressor analysis

    PMID:28784717

    Open questions at the time
    • Binding interface between Gle1 and Ded1 not mapped
    • In vivo transcriptome-wide impact on Ded1 targets not profiled
  12. 2018 High

    Quantitative kinetic analysis revised the Dbp5 catalytic cycle: Gle1 slows ADP release rather than Nup159 accelerating it, and Nup159 instead weakens Gle1-Dbp5(ADP) interaction to promote Gle1 release, redefining the roles of both cofactors.

    Evidence Solution-based kinetic and thermodynamic nucleotide binding assays

    PMID:29782832

    Open questions at the time
    • Whether this revised model holds under NPC-proximal crowding conditions not tested
  13. 2018 High

    Discovery that MAPK (ERK/JNK) and GSK3 phosphorylate Gle1A's N-terminal domain during stress, modulating self-association, DDX3 inhibition, and stress granule dynamics, revealed a signaling input that toggles Gle1's cytoplasmic functions.

    Evidence Mass spectrometry of phosphorylation sites, in vitro kinase assays, phosphomimetic/phosphodeficient mutant SG phenotypes

    PMID:30429220

    Open questions at the time
    • Phosphatase(s) responsible for dephosphorylation not identified
    • Whether phosphorylation also affects mRNA export function not tested
  14. 2020 Medium

    Identification of two independent self-association regions (coiled-coil and a 10-aa aggregation-prone motif), both required for mRNA export and stress granule formation but dispensable for basal translation, dissected which Gle1 functions require oligomerization.

    Evidence Mutagenesis of oligomerization domains with functional assays in HeLa cells for export, SG formation, and translation

    PMID:32981894

    Open questions at the time
    • Relative contribution of each domain to oligomer architecture not structurally resolved
  15. 2020 Medium

    Revealing that Gle1 shuttling disruption causes nuclear mRNA accumulation through altered transcription state (not export block), via reduced DDX1 interaction with CstF-64 and increased R-loops, established a nuclear role for Gle1 in transcription termination and 3′-end processing.

    Evidence Peptide-mediated shuttling inhibition, RNA-seq, co-IP of DDX1/CstF-64, R-loop immunofluorescence

    PMID:32755435

    Open questions at the time
    • Direct enzymatic activity of Gle1 on DDX1 not biochemically demonstrated
    • Genome-wide sites of Gle1-dependent transcription termination not mapped
  16. 2022 High

    Definitive kinetic dissection showed Gle1 activates Dbp5 by two synergistic mechanisms—coupling Gle1 binding to ATP binding (>100-fold selectivity) and accelerating Pi release ~20-fold—providing the most complete mechanistic picture of Gle1-dependent helicase activation.

    Evidence Stopped-flow and steady-state fluorescence-based nucleotide binding and ATPase assays

    PMID:35286399

    Open questions at the time
    • Whether these kinetic parameters change when Dbp5 is RNA-loaded at the NPC not tested
    • Structural basis for preferential ATP-state binding not visualized
  17. 2024 Medium

    Demonstrating that Gle1-Dbp5 interaction is required for tRNA export and that tRNA synergizes with Gle1 to activate Dbp5 expanded Gle1's role beyond mRNA to a broader RNA export regulator.

    Evidence In vivo co-IP, dominant-negative Dbp5 overexpression epistasis, in vitro ATPase assays with tRNA substrates

    PMID:38189406

    Open questions at the time
    • Whether Gle1-Dbp5 acts on tRNA at the NPC or in the nucleoplasm not resolved
    • Specific tRNA species affected not profiled

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the full Gle1-Dbp5 complex (ideally with IP6, Nup42, and RNA) is needed to explain how Gle1 differentially activates Dbp5 while inhibiting Ded1/DDX3, and how disease mutations structurally disrupt these interactions.
  • No co-crystal or cryo-EM structure of the full Gle1-Dbp5-Nup42-IP6 complex
  • Structural basis for Gle1 activation versus inhibition of different DEAD-box helicases unknown
  • How Gle1 oligomeric architecture integrates into the intact NPC scaffold not visualized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 2 GO:0005635 nuclear envelope 2 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
DBP5DDX1DDX19BDDX3MKRN2NUP155NUP42NUPL2
Complex memberships
Gle1–Gfd1–Nab2 export complexNup155–hCG1–Gle1B NPC subcomplexNup42–Gle1–Dbp5 trimeric complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Gle1 and inositol hexakisphosphate (InsP6/IP6) together stimulate the RNA-dependent ATPase activity of the DEAD-box protein Dbp5 at the nuclear pore complex cytoplasmic face to mediate directional mRNA export; Gle1 alone has minimal effect, InsP6 requires Gle1, and maximal InsP6 binding requires both Dbp5 and Gle1. In vitro ATPase kinetic assays, genetic epistasis (DBP5 overexpression suppresses ipk1 nup42 mutant defects), in vitro binding assays Nature cell biology High 16783363 16783364
2006 Gle1 binds directly to InsP6, and this interaction potentiates Gle1-mediated stimulation of Dbp5 ATPase and RNA binding; a gle1 point mutant deficient for Dbp5 stimulation in vitro displays mRNA export defects in vivo. In vitro ATPase assays, direct binding assays, in vivo mRNA export analysis of gle1 point mutants Nature cell biology High 16783363 16783364
2008 Gle1 and IP6 are required for efficient translation termination in S. cerevisiae and Gle1 physically interacts with translation termination factors; additionally, Gle1 has a conserved physical association with initiation factor eIF3 and gle1 mutants display genetic interactions with the eIF3 mutant nip1-1, indicating a role in translation initiation independent of IP6. Co-immunoprecipitation, genetic interaction analysis, in vivo translation assays Cell High 18724935
2010 Specific Gle1 residues constituting the IP6 binding pocket are required for IP6-dependent Dbp5 stimulation in vitro; IP6-binding Gle1 mutants recapitulate all mRNA export and translation termination defects of IP6-depleted cells, establishing Gle1 as the primary target of IP6 for both processes. In vitro ATPase stimulation assays with Gle1 point mutants, in vivo mRNA export and translation termination assays The Journal of biological chemistry High 20371601
2011 Nup159 is required for ADP release from Dbp5, while Gle1-IP6 stimulates ATP binding and primes Dbp5 for RNA loading, allowing multiple cycles of mRNP remodeling by a single Dbp5 at the NPC; Nup159 and Gle1-IP6 together regulate the nucleotide-bound state of Dbp5. In vitro reconstitution ATPase assays, dbp5 mutant analysis, in vivo mRNA export assays Genes & development High 21576265 21576266
2011 The Dbp5-Gle1 interaction is limiting for mRNA export and can be independent of Nup159; RNA-binding-deficient Dbp5 mutants act as dominant negatives by competing with wild-type Dbp5 for Gle1 at NPCs; ATP binding and hydrolysis are required for efficient Dbp5 association with NPCs; Dbp5 association with NPCs is very dynamic (<1 sec by FRAP). Dominant-negative mutant analysis, in vivo mRNA export assays, FRAP in yeast and human cells Genes & development High 21576265
2011 Gle1 physically and genetically interacts with the DEAD-box protein Ded1 and inhibits Ded1 ATPase activity in vitro in an IP6-independent manner, thereby negatively regulating translation initiation; a gle1-4 mutant suppresses initiation defects in ded1-120. Co-immunoprecipitation, in vitro ATPase inhibition assays, genetic suppressor analysis, in vitro translation assays The Journal of biological chemistry High 21949122
2009 Crystal structure of the C-terminal domain of Dbp5 (1.8 Å) revealed the Gle1 interaction surface; structure-guided mutagenesis identified charged surface residues whose mutation weakens Gle1 binding and inhibits Gle1-stimulated ATPase activity, with the weakest mutants unable to support yeast growth. X-ray crystallography, structure-guided mutagenesis, in vitro ATPase assays, in vivo complementation Proceedings of the National Academy of Sciences of the United States of America High 19805289
2013 Gle1 self-associates via its coiled-coil domain to form ~26 nm diameter disk-shaped oligomeric particles visible by electron microscopy; the LCCS1 disease mutation FinMajor (PFQ insertion in the coiled-coil domain) causes malformed oligomeric particles and specifically impairs mRNA export but not translation functions of Gle1. Electron microscopy, in vitro self-association assays, in vivo functional assays for mRNA export and translation, FinMajor mutant analysis Cell High 24243016
2005 The hGle1B isoform-specific C-terminal 43 amino acid region mediates binding to the nucleoporin hCG1/NPL1; hNup155, hGle1B, and hCG1 form a heterotrimeric complex in vitro; siRNA-mediated depletion of hCG1 results in hGle1 accumulation in cytoplasmic foci and inhibition of Hsp70 mRNA export. In vitro binding assays, heterotrimeric complex reconstitution, siRNA knockdown, mRNA export assays Molecular biology of the cell High 16000379
2003 hGle1 (hGle1B isoform) localizes to the nuclear envelope/NPC; hGle1 shuttles between nucleus and cytoplasm via an internal 39-amino acid shuttling domain; disruption of shuttling by a cell-permeable peptide impairs bulk poly(A)+ mRNA export and specific mRNA export, reducing hGle1 localization at the NE. Live cell FRAP, microinjection of recombinant protein, cell-permeable shuttling domain peptide, mRNA export assays The Journal of cell biology High 12668658
2003 hGle1 physically interacts with the nucleoporin hNup155; the N-terminal 29 residues of hGle1 constitute the hNup155-binding domain and are required for nuclear rim/NPC localization of hGle1B. Yeast two-hybrid screen, in vitro binding assays, deletion analysis, localization studies in HeLa cells Molecular & cellular proteomics Medium 14645504
2004 Cytoplasmic IP6 production is sufficient to mediate the Gle1-mRNA export pathway; genetic epistasis placed IP6 action at a cytoplasmic step involving Nup42, Nup159, Dbp5, and Gle2 but not FG-repeat domains of nucleoporins. Genetic epistasis with ipk1 null double mutants, spatial restriction of Ipk1 to cytoplasm, complementation assays The Journal of biological chemistry Medium 15459192
2004 Nab2, Gfd1, and Gle1 associate in a complex; Gfd1 directly binds Nab2 at its N-terminal domain (distinct from RNA-binding domains), and Gfd1 bridges Gle1 and Nab2-bound mRNA during export; Nab2 export is blocked in gle1 mutants. Pulldown with recombinant proteins, co-immunoprecipitation from yeast lysates, two-hybrid assays, in vivo export analysis The Journal of biological chemistry Medium 15208322
2017 Nup42's C-terminal domain binds Gle1/hGle1B at an interface distinct from the Gle1-Dbp5 interaction site; a trimeric Nup42-CTD/Gle1-CTD/Dbp5 complex forms in the presence of IP6; Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5/DDX19B in vitro in a non-additive manner; deletion of NUP42 abrogates Gle1-Dbp5 interaction and disruption of Nup42 or IP6 binding sites causes mRNA export defects in yeast and human cells. In vitro ATPase stimulation assays, trimeric complex formation, structure-function mutagenesis in yeast and human cells, mRNA export assays Traffic (Copenhagen, Denmark) High 28869701
2018 Human Gle1 is phosphorylated during heat shock stress by MAPKs ERK and JNK, which phosphorylate the Gle1A N-terminal domain and prime it for further phosphorylation by GSK3; phosphomimetic gle1A6D perturbs self-association and inhibits DDX3 ATPase activity; phosphodeficient GFP-gle1A6A promotes stress granule (SG) assembly whereas phosphomimetic GFP-gle1A6D enhances SG disassembly. MS identification of phosphorylation sites, in vitro kinase assays, ATPase inhibition assays, GFP-tagged phosphomimetic/phosphodeficient mutant expression with SG phenotype readout The Journal of biological chemistry High 30429220
2022 Gle1 activates Dbp5 ATPase by two mechanisms: (1) thermodynamically coupling Gle1 binding to ATP binding on Dbp5 (Gle1 binds Dbp5-ATP >100-fold more tightly than other nucleotide states; Gle1 increases ATP equilibrium binding >150-fold by slowing ATP dissociation), and (2) accelerating the rate-limiting Pi release step ~20-fold. Kinetic and equilibrium ATPase analyses (stopped-flow and steady-state), fluorescence-based nucleotide binding assays Nucleic acids research High 35286399
2018 Nup159 does not accelerate ADP release from Dbp5; instead, Gle1 slows ADP release from Dbp5 independent of Mg2+; in the presence of Nup159, Gle1 interaction with ADP-bound Dbp5 is reduced ~18-fold, suggesting Nup159 modulates the Dbp5-Gle1 interaction to aid Gle1 release rather than acting as a nucleotide exchange factor. In vitro solution-based kinetic and thermodynamic ATPase/nucleotide binding assays Journal of molecular biology High 29782832
2017 Gle1 inhibits Ded1 by reducing Ded1's affinity for RNA; this inhibition counteracts excess Ded1-mediated translation repression, positioning Gle1 as a gatekeeper to optimize Ded1 activity; both Ded1 and Gle1 affect preinitiation complex assembly. RNA binding assays (mutation analysis), in vitro translation assays, in vivo genetic suppressor analysis Molecular and cellular biology Medium 28784717
2016 Gle1 is enriched at the centrosome and basal body, assembling into the toroid-shaped pericentriolar material around the mother centriole; reduced Gle1 levels correlate with decreased pericentrin at the centrosome and microtubule organization defects not caused by loss of mRNA export; Gle1 depletion in zebrafish compromises ciliary beating in Kupffer's vesicle. Immunofluorescence localization, siRNA knockdown with microtubule phenotype readout, zebrafish morpholino depletion Molecular biology of the cell Medium 28035044
2020 Gle1 self-association is driven by two distinct regions: a coiled-coil domain and a novel 10-amino acid aggregation-prone region; both are required for proper mRNA export and stress granule formation; Gle1 oligomerization is dispensable for non-stressed translation initiation but both self-association domains are independently required for translation regulation under cellular stress. Mutagenesis of oligomerization domains, functional assays in HeLa cells for mRNA export, stress granule formation, and translation The Journal of biological chemistry Medium 32981894
2020 Disruption of Gle1 nucleocytoplasmic shuttling causes nuclear accumulation of specific mRNAs with elongated 3'-UTRs due to changes in transcription state (not altered nuclear export); shuttling inhibition results in increased DDX1 nucleoplasmic localization, decreased DDX1 interaction with Gle1 and the pre-mRNA cleavage factor CstF-64, and increased nuclear R-loop signal; Gle1 colocalizes with R-loops, revealing a nuclear role in coordinating DDX1 function in transcription termination. Peptide-mediated shuttling disruption, RNA sequencing, immunofluorescence, co-immunoprecipitation, R-loop detection Molecular biology of the cell Medium 32755435
2020 The RNA-binding E3 ubiquitin ligase MKRN2 physically interacts with GLE1; MKRN2 knockdown or knockout in zebrafish partially rescues retinal developmental defects caused by GLE1 depletion, indicating MKRN2 is epistatic to GLE1; MKRN2 knockdown enhances nuclear export of MKRN2-associated mRNAs. Affinity-purification mass spectrometry, zebrafish morpholino knockdown and CRISPR knockout with epistasis analysis, ribonomic (RIP) assays Cell reports Medium 32460013
2024 Gle1 binding to Dbp5 is required for Dbp5 to direct tRNA export in vivo; tRNA (or dsRNA) does not itself activate Dbp5 ATPase activity but acts synergistically with Gle1 to fully activate Dbp5; Dbp5 is recruited to tRNA independently of canonical mRNA export factors Los1, Msn5, or Mex67. Co-immunoprecipitation (in vivo), Dbp5 dominant-negative overexpression epistasis, in vitro ATPase assays with tRNA eLife Medium 38189406
2023 Phosphorylation of Gle1 at threonine 102 (T102) serves as a priming event for further phosphorylation in Gle1's N-terminal low complexity cluster; basally phosphorylated (pT102) Gle1 is predominantly nuclear with punctate distribution; under sodium arsenite stress, pT102-Gle1 shifts to cytoplasm; pT102-Gle1 co-immunoprecipitates with DDX1 in a phosphatase-sensitive manner, linking phosphorylation to Gle1's role in regulating DDX1 during transcription termination. In vitro kinase assays, phospho-specific antibody immunofluorescence microscopy, co-immunoprecipitation Advances in biological regulation Medium 37801910
2025 Crystal structure of N-terminally truncated Gle1 from Debaryomyces hansenii (DhGle1ΔN) was determined at 1.5 Å resolution, revealing 13 α-helices and a RecA-like fold; comparison with homolog structures in complexes identifies distinct secondary structural elements in α1, α3, α4, and α8 that may relate to Dbp5 interaction. X-ray crystallography at 1.5 Å resolution International journal of molecular sciences Medium 40004126

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nature cell biology 239 16783363
2006 Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nature cell biology 226 16783364
2008 Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. Nature genetics 152 18204449
2008 The mRNA export factor Gle1 and inositol hexakisphosphate regulate distinct stages of translation. Cell 126 18724935
2014 Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. Human molecular genetics 114 25343993
2011 The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. Genes & development 93 21576266
2011 The Dbp5 cycle at the nuclear pore complex during mRNA export I: dbp5 mutants with defects in RNA binding and ATP hydrolysis define key steps for Nup159 and Gle1. Genes & development 91 21576265
2011 Dbp5, Gle1-IP6 and Nup159: a working model for mRNP export. Nucleus (Austin, Tex.) 86 22064466
2013 Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease. Cell 70 24243016
2010 Control of mRNA export and translation termination by inositol hexakisphosphate requires specific interaction with Gle1. The Journal of biological chemistry 70 20371601
2005 Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin hCG1: a conserved mechanism in the export of Hsp70 mRNA. Molecular biology of the cell 69 16000379
2003 The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155. Molecular & cellular proteomics : MCP 54 14645504
2003 An essential role for hGle1 nucleocytoplasmic shuttling in mRNA export. The Journal of cell biology 52 12668658
2012 A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. Development (Cambridge, England) 46 22357925
2004 Cytoplasmic inositol hexakisphosphate production is sufficient for mediating the Gle1-mRNA export pathway. The Journal of biological chemistry 45 15459192
2015 InsP6-sensitive variants of the Gle1 mRNA export factor rescue growth and fertility defects of the ipk1 low-phytic-acid mutation in Arabidopsis. The Plant cell 40 25670768
2017 Nup42 and IP6 coordinate Gle1 stimulation of Dbp5/DDX19B for mRNA export in yeast and human cells. Traffic (Copenhagen, Denmark) 39 28869701
2011 Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in translation initiation. The Journal of biological chemistry 38 21949122
2004 Nuclear export of the yeast mRNA-binding protein Nab2 is linked to a direct interaction with Gfd1 and to Gle1 function. The Journal of biological chemistry 32 15208322
2016 A role for Gle1, a regulator of DEAD-box RNA helicases, at centrosomes and basal bodies. Molecular biology of the cell 30 28035044
2009 Structure of the C-terminus of the mRNA export factor Dbp5 reveals the interaction surface for the ATPase activator Gle1. Proceedings of the National Academy of Sciences of the United States of America 30 19805289
2015 Restoration of miR-127-3p and miR-376a-3p counteracts the neoplastic phenotype of giant cell tumor of bone derived stromal cells by targeting COA1, GLE1 and PDIA6. Cancer letters 26 26655997
2013 Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis. Advances in biological regulation 25 24275432
2015 An amyotrophic lateral sclerosis-linked mutation in GLE1 alters the cellular pool of human Gle1 functional isoforms. Advances in biological regulation 23 26776475
2018 MAPK- and glycogen synthase kinase 3-mediated phosphorylation regulates the DEAD-box protein modulator Gle1 for control of stress granule dynamics. The Journal of biological chemistry 22 30429220
2018 Depletion of mRNA export regulator DBP5/DDX19, GLE1 or IPPK that is a key enzyme for the production of IP6, resulting in differentially altered cytoplasmic mRNA expression and specific cell defect. PloS one 19 29746542
2017 Gle1 Regulates RNA Binding of the DEAD-Box Helicase Ded1 in Its Complex Role in Translation Initiation. Molecular and cellular biology 19 28784717
2017 Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum. Clinical genetics 16 27684565
2018 Gle1 mediates stress granule-dependent survival during chemotoxic stress. Advances in biological regulation 15 30262214
2020 MKRN2 Physically Interacts with GLE1 to Regulate mRNA Export and Zebrafish Retinal Development. Cell reports 14 32460013
2022 The nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release. Nucleic acids research 11 35286399
2017 Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1. American journal of medical genetics. Part A 11 28884921
2018 Nup159 Weakens Gle1 Binding to Dbp5 But Does Not Accelerate ADP Release. Journal of molecular biology 10 29782832
2020 Functions of Gle1 are governed by two distinct modes of self-association. The Journal of biological chemistry 9 32981894
2016 A mitotic nuclear envelope tether for Gle1 also impacts nuclear and nucleolar architecture. Molecular biology of the cell 9 27630260
2016 Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. Neuroscience 8 26921650
2017 The importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis. Cold Spring Harbor molecular case studies 6 28729373
2008 Gle1 does double duty. Cell 6 18724928
2017 A homozygous I684T in GLE1 as a novel cause of arthrogryposis and motor neuron loss. Clinical genetics 5 28657126
2020 Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites. Molecular biology of the cell 4 32755435
2020 Extension of the phenotypic spectrum of GLE1-related disorders to a mild congenital form resembling congenital myopathy. Molecular genetics & genomic medicine 3 32537934
2019 Correction: Depletion of mRNA export regulator DBP5/DDX19, GLE1 or IPPK that is a key enzyme for the production of IP6, resulting in differentially altered cytoplasmic mRNA expression and specific cell defect. PloS one 3 31344122
2024 Gle1 is required for tRNA to stimulate Dbp5 ATPase activity in vitro and promote Dbp5-mediated tRNA export in vivo in Saccharomyces cerevisiae. eLife 2 38189406
2021 Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients. Frontiers in neuroscience 2 34025336
2018 Screening of GLE1 mutations in Chinese amyotrophic lateral sclerosis patients. Neurobiology of aging 2 29398120
2023 Gle1 is required for tRNA to stimulate Dbp5 ATPase activity in vitro and to promote Dbp5 mediated tRNA export in vivo. bioRxiv : the preprint server for biology 1 37425677
2018 The expression of SMN1, MART3, GLE1 and FUS genes in spinal muscular atrophy. Folia histochemica et cytobiologica 1 30565205
2025 Molecular Structure of the mRNA Export Factor Gle1 from Debaryomyces hansenii. International journal of molecular sciences 0 40004126
2023 Phosphorylation impacts GLE1 nuclear localization and association with DDX1. Advances in biological regulation 0 37801910