| 2006 |
DDX39A (DDX39) is ubiquitylated and its stability is regulated via the ubiquitin-proteasome pathway; it tethers ALY (an mRNA export factor) in vivo; CIP29 was identified as a main DDX39-interacting protein by Co-IP and mass spectrometry, and CIP29 binds RNA on its own and enhances the RNA unwinding activity of DDX39; FUS/TLS was identified as a CIP29-interacting protein, placing DDX39 in a network with ALY, CIP29, and FUS/TLS in transcription, splicing, and RNA export. |
Co-immunoprecipitation, mass spectrometry, in vivo ubiquitylation assay, RNA unwinding activity assay |
Experimental cell research |
High |
17196963
|
| 2007 |
Recombinant DDX39A (DDX39-L) binds RNA, hydrolyzes NTPs in an RNA-dependent manner, and unwinds double-stranded RNA bidirectionally, confirming it is a bona fide RNA helicase with ATPase activity; punctate nuclear localization suggests a role in RNA splicing/export. |
Recombinant protein biochemistry: RNA-binding assay, NTPase assay, RNA unwinding assay; nuclear localization by fluorescence microscopy |
Cancer biology & therapy |
High |
17548965
|
| 2010 |
UAP56 (DDX39B) forms the human TREX complex, whereas URH49 (DDX39A) forms a distinct AREX complex with CIP29; genome-wide mRNA targets regulated by each helicase are different, with each controlling distinct subsets of mitotic regulators. Depletion of URH49/DDX39A causes chromosome arm resolution defects and cytokinesis failure, whereas depletion of CIP29 phenocopies URH49 depletion. |
RNAi knockdown, genome-wide mRNA profiling, fluorescence microscopy of mitotic phenotypes, Co-IP to define complex composition |
Molecular biology of the cell |
High |
20573985
|
| 2004 |
URH49 (DDX39A) interacts with the mRNA export factor Aly and can rescue loss of Sub2p (yeast UAP56 homolog), demonstrating functional conservation in mRNA splicing and nuclear export. |
Yeast complementation assay, Co-immunoprecipitation with Aly |
Nucleic acids research |
High |
15047853
|
| 2006 |
siRNA-mediated reduction of URH49 (DDX39A) expression leads to nuclear accumulation of poly(A)+ mRNA in a speckled pattern, demonstrating its essential role in nuclear mRNA export; combined depletion of both UAP56 and URH49 causes cell death and major mRNA export block. |
RNAi knockdown, fluorescence in situ hybridization (FISH) of poly(A)+ RNA |
Gene |
High |
16949219
|
| 2011 |
DDX39A directly interacts with the TRFH domain of TRF2 via an FXLXP motif and is also found in association with catalytically competent telomerase through interaction with hTERT; overexpression causes progressive telomere elongation while shRNA-mediated depletion causes telomere shortening, DNA-damage foci at telomeres, and aberrant telomere structure. |
Co-immunoprecipitation, motif mapping, shRNA knockdown, telomere FISH, telomere length assay, telomere dysfunction-induced foci (TIF) assay |
Aging cell |
High |
21388492
|
| 2011 |
MxA (antiviral GTPase) directly interacts with URH49 (DDX39A) and UAP56 in vitro using purified recombinant proteins; MxA-URH49 complexes localize to the perinuclear region, suggesting MxA exerts antiviral activity by sequestering these RNA helicases. |
Immunoprecipitation, in vitro binding assay with purified recombinant proteins, co-localization by fluorescence microscopy |
The Journal of biological chemistry |
High |
21859714
|
| 2011 |
UAP56 and URH49 (DDX39A) exhibit CRM1-independent nucleocytoplasmic shuttling activity; the shuttling region of UAP56 maps to C-terminal amino acids 195–428; the region required for intranuclear localization maps to aa 81–381; interaction with REF requires aa 51–428; human UAP56 shuttles independently of Rae1. |
Domain mapping with truncation/chimeric mutants, heterokaryon shuttling assay, co-localization studies |
PloS one |
Medium |
21799930
|
| 2020 |
DDX39A is SUMOylated by SUMO1, 2, and 3; RanBP2 acts as an E3 SUMO1 ligase for DDX39A and enhances SUMO1 modification, which attenuates DDX39A's ability to bind RNA. Viral infection reduces RanBP2-mediated SUMO1 modification of DDX39A, increasing DDX39A binding to TRAF3, TRAF6, and MAVS mRNAs, sequestering them in the nucleus and suppressing innate immune signaling. |
Co-immunoprecipitation, SUMO modification assays, RNAi knockdown, RNA immunoprecipitation, nuclear/cytoplasmic fractionation |
Journal of immunology |
High |
32393512
|
| 2020 |
URH49 (DDX39A) forms an Apo-AREX complex containing CIP29 but not ALYREF or the THO subcomplex in ATP-depleted conditions; upon ATP addition, the Apo-AREX complex is remodeled to an ATP-TREX-like complex containing THO subcomplex, ALYREF, and CIP29; URH49-dependent mRNA export is achieved through NXF1. |
ATP depletion/addition complex assembly assays, Co-IP, knockdown with cytokinesis phenotype readout |
Biochimica et biophysica acta. Gene regulatory mechanisms |
High |
31917363
|
| 2016 |
Simultaneous knockdown of DDX39A and its paralog DDX39B drastically and selectively downregulates AR-V7 mRNA expression in AR-V7-positive prostate cancer cell lines, identifying DDX39A as a regulator of androgen receptor splice variant generation. |
shRNA library screen, RNAi knockdown, RT-PCR/qPCR |
Biochemical and biophysical research communications |
Medium |
28025139
|
| 2018 |
DDX39A overexpression increases β-catenin nuclear accumulation and upregulates Wnt/β-catenin target genes in HCC cells; knockdown of TCF4 and LEF1 in DDX39A-overexpressing cells inhibits Wnt pathway target genes and reduces invasion, placing DDX39A upstream of β-catenin/TCF4/LEF1 in Wnt signaling. |
Overexpression and knockdown studies, nuclear/cytoplasmic fractionation, Western blot, Wnt target gene RT-PCR, co-knockdown epistasis |
Cell death & disease |
Medium |
29867138
|
| 2021 |
ECD (mammalian ecdysoneless protein) physically interacts with DDX39A and is required for mRNA nuclear export; ECD knockdown blocks mRNA nuclear export, which is rescued by full-length ECD but not by an ECD mutant defective in DDX39A interaction, establishing DDX39A as a functional partner of ECD in mRNA export. |
Co-immunoprecipitation, knockdown rescue experiment, FISH for mRNA localization |
Molecular and cellular biology |
High |
33941617
|
| 2023 |
Upon chikungunya virus (CHIKV) infection, the predominantly nuclear DDX39A accumulates in the cytoplasm; DDX39A binds CHIKV genomic RNA, specifically interacting with the 5' conserved sequence element (5'CSE), and this interaction is essential for antiviral activity; DDX39A inhibits alphavirus replication independently of the canonical interferon pathway. |
Genetic screen, RNAi/overexpression functional assays, RNA immunoprecipitation, biochemical binding assays, live-cell imaging of relocalization, IFN-independent antiviral assay |
Molecular cell |
High |
37949067
|
| 2024 |
Upon replication stress, DDX39A resolves RNA-DNA hybrids at stalled replication forks; DDX39A is a RAD51-associated protein that binds stalled forks and unwinds replication fork-associated RNA-DNA hybrids (RF-RDs), facilitating regulated DNA2-mediated DNA resection and fork restart; loss of DDX39A enhances fork protection in BRCA1/2-deficient cells, conferring chemoresistance. |
Co-immunoprecipitation with RAD51, proximity ligation assays at forks, DNA fiber assay, DRIP-seq (RNA-DNA hybrid mapping), DDX39A knockdown/overexpression with fork restart readouts |
Molecular cell |
High |
39706185 39706186
|
| 2024 |
DDX39A (URH49) loads PHAX onto U snRNA in an ATP-dependent manner, stimulating RNA binding of PHAX (a U snRNA export adapter), thereby facilitating spliceosomal U snRNA nuclear export; ALYREF acts as a bridge between PHAX and UAP56/DDX39B in this pathway. |
In vitro reconstitution assay for ATP-dependent U snRNA export factors, RNA-protein loading assay, Co-IP |
Nucleic acids research |
High |
39011894
|
| 2024 |
DDX39A and DDX39B have significant redundancy in alternative splicing targets genome-wide, but specific pre-mRNAs require one or the other paralog; DDX39A cannot complement DDX39B-dependent splicing of IL7R exon 6; cassette exons specifically dependent on DDX39B have U-poor/C-rich polypyrimidine tracts upstream, establishing this sequence feature as a determinant of DDX39B (not DDX39A) dependency. |
RNAi knockdown, RNA-seq, splicing minigene assays, paralog-specific complementation |
Nucleic acids research |
High |
38801080
|
| 2024 |
SNRPD2 (PD2), together with HNRNPL, modulates DDX39A intron retention to produce a short DDX39A variant (39A_S); 39A_S mediates MYC mRNA nuclear export to maintain high MYC protein expression; MYC in turn potentiates PD2 transcription, forming a positive feedback loop in HCC. |
RNA-seq, RIP-qPCR, Co-IP, mRNA export fractionation assay, knockdown/overexpression, xenograft models |
Advanced science |
Medium |
39018261
|
| 2024 |
UAP56 (DDX39B) and URH49 (DDX39A) have distinct structural features in their apo forms that determine their respective complex formation (apo-TREX vs apo-AREX); chimeric mutant analysis identified that the terminal regions of UAP56 and the C-terminal region of URH49 are indispensable for their respective complex assembly, and a specific C-terminal amino acid in UAP56 is critical for its complex formation and mRNA export activity. |
Crystal/structural analysis of UAP56 and URH49, chimeric mutant construction, Co-IP complex assembly assays, mRNA export assays |
Nature communications |
High |
38225262
|
| 2024 |
In mouse ESCs, Erk2 phosphorylates Ddx39 on Y132 and Y138; phosphorylated Ddx39 promotes recruitment of Hat1 to acetylate H3K27 and activate differentiation genes; Ddx39 is recruited to telomeres by Trf1, disrupts Trf1-mediated DNA loops and suppresses ALT activity; phosphorylation of Ddx39 by Erk2 weakens its interaction with Trf1, releasing it from telomeres and allowing ALT-mediated telomere elongation. |
Co-IP/MS for Erk2 interactors, in vitro kinase assay, Ddx39 KO ESCs, ChIP, H3K27ac analysis, telomere FISH/CO-FISH for ALT activity |
Cell death and differentiation |
High |
39107495
|
| 2025 |
A pathogenic DDX39A variant (K137Q) fails to interact with the TREX component THOC1, destabilizing TREX complex integrity; mutant DDX39A-K137Q displays aberrant nuclear clumping rather than normal nuclear distribution; structural modeling shows Lys137 mediates critical inter- and intra-molecular interactions disrupted by K137Q substitution; mutant cells show nuclear lamina disorganization and increased cell death. |
Patient-derived fibroblast functional studies, Co-IP (DDX39A-K137Q vs THOC1), structural modeling, nuclear morphology analysis, transcriptomic analysis |
Clinical genetics |
Medium |
40726340
|
| 2026 |
DDX39A directly binds SP1 mRNA, stabilizing it and enhancing SP1 translation efficiency; increased SP1 protein then transcriptionally activates Ku70 (a key NHEJ component) by binding the −223/−214 bp region of the Ku70 promoter, contributing to radioresistance in ESCC; this DDX39A–SP1–Ku70 axis is necessary and sufficient to mediate radioresistance. |
RIP-qPCR (DDX39A binding to SP1 mRNA), ChIP-qPCR (SP1 on Ku70 promoter), dual-luciferase reporter assay, knockdown/rescue, proteomics, xenograft models |
Cellular oncology |
Medium |
41984289
|
| 2026 |
DDX39A regulates alternative splicing of WISP1 pre-mRNA, stabilizing it; DDX39A KD reduces the oncogenic WISP1 isoform, suppressing AKT signaling; secreted WISP1 acts as a paracrine signal promoting immunosuppressive tumor-associated macrophage polarization; Fluphenazine hydrochloride binds to and inhibits DDX39A. |
RNA-seq, RIP-seq, knockdown in vitro and in vivo, WISP1 isoform analysis, AKT pathway readouts, macrophage co-culture assay, drug-target interaction (binding assay) |
Oncogene |
Medium |
41772197
|
| 2025 |
DDX39A promotes exon skipping of ITGA6 pre-mRNA to produce the oncogenic ITGA6A transcript; SNRPB depletion induces DDX39A intron retention at introns 6 and 8, generating a noncoding transcript subject to nonsense-mediated decay; DDX39A knockdown reduces proliferative and metastatic capacities downstream of SNRPB overexpression. |
RNA-seq (splicing analysis), RNAi knockdown, antisense oligonucleotide silencing, CDX/PDX models, epistasis between SNRPB and DDX39A |
Oncogene |
Medium |
40216968
|