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Showing DDX39B — UAP56 is a alias.

DDX39B

Spliceosome RNA helicase DDX39B · UniProt Q13838

Length
428 aa
Mass
49.0 kDa
Annotated
2026-06-09
70 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX39B/UAP56 is a conserved DEAD-box ATP-dependent RNA helicase that couples nuclear mRNA biogenesis to export and safeguards genome integrity by resolving aberrant nucleic acid structures (PMID:11675789, PMID:15585580, PMID:32439635). Crystal and cryo-EM structures reveal two RecA-like helicase domains that undergo ADP-induced conformational changes, supporting an RNA-stimulated ATPase that hydrolyzes only ATP and an ATP-dependent helicase that unwinds RNA duplexes with diverse end structures (PMID:15585580, PMID:15296731, PMID:17562711). Through ATP-dependent loading of the export adaptor Aly/REF onto both spliced and intronless mRNAs, DDX39B bridges splicing and export by nucleating the human TREX complex, in which it directly links Aly and CIP29/SARNP; loss of DDX39B causes nuclear retention of poly(A)+ RNA and is essential across metazoa (PMID:11675789, PMID:11696332, PMID:17984224, PMID:20844015). SARNP engages DDX39B through tandem motifs to build a high-order multivalent mRNP, and release of DDX39B from the export-competent mRNP is governed at the nuclear pore by TREX-2 and the related TREX-2.1 (LENG8-PCID2-DSS1) complex, which together direct GC-rich transcripts toward export (PMID:37578863, PMID:40595470). Beyond export, DDX39B promotes pre-spliceosome assembly on introns bearing C-rich/U-poor polypyrimidine tracts—such as those in FOXP3 and IL7R—conferring substrate-specific dependence not shared with its paralog DDX39A (PMID:37261960, PMID:38575347, PMID:38801080). As a cotranscriptional RNA-DNA helicase it unwinds R-loops genome-wide to prevent transcription-replication conflicts and replication fork stalling, and it represses A-to-I RNA editing by limiting double-stranded RNA accumulation (PMID:32439635, PMID:40652511). DDX39B is post-translationally controlled by Plk1-dependent phosphorylation and PIASx-β-mediated sumoylation that trigger its ubiquitination and degradation, while its abundance and TREX assembly depend on specific terminal residues (PMID:21637952, PMID:32209106, PMID:38377942). In addition to its cellular roles, DDX39B acts as a chaperone for influenza nucleoprotein, promoting trimeric NP formation and viral RNP assembly (PMID:29070793, PMID:32085897). De novo DDX39B variants that impair TREX interaction cause aberrant splicing and developmental defects in patients and animal models, linking the gene to a neurodevelopmental disorder (PMID:39918047).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Established how splicing is mechanistically coupled to mRNA export by showing DDX39B recruits the export adaptor Aly/REF onto spliced mRNPs.

    Evidence Reciprocal Co-IP, dominant-negative overexpression, and interaction-blocking mutagenesis in Xenopus and mammalian systems

    PMID:11675789

    Open questions at the time
    • ATP-dependence of Aly recruitment not yet resolved at this stage
    • Intronless mRNA handling not addressed
  2. 2001 High

    Defined DDX39B as an essential bulk mRNA export factor, linking its loss to global nuclear poly(A)+ RNA retention.

    Evidence RNAi depletion in Drosophila with nuclear fractionation, protein synthesis measurement, and human spliced-mRNP association

    PMID:11696332

    Open questions at the time
    • Molecular mechanism of release at the pore not addressed
    • Helicase activity not yet biochemically demonstrated
  3. 2001 Medium

    Identified DDX39B as an influenza NP-interacting host factor that promotes NP-RNA complex formation, revealing a viral-hijacking function.

    Evidence Yeast two-hybrid, in vitro binding, and biochemical viral RNA synthesis assays

    PMID:11160689

    Open questions at the time
    • Structural basis of NP recognition unresolved at this stage
    • Single-lab finding
  4. 2004 High

    Provided the structural framework: two RecA-like helicase domains with an ADP-responsive nucleotide pocket and validated RNA-dependent ATPase activity.

    Evidence X-ray crystallography of apo, ADP-bound, and mutant forms plus in vitro ATPase assays, replicated by an independent structure

    PMID:15296731 PMID:15585580

    Open questions at the time
    • Conformational cycle on RNA substrate not captured
    • Coupling of structure to TREX assembly not yet shown
  5. 2007 High

    Resolved the enzymology: DDX39B is an ATP-specific RNA-stimulated ATPase and ATP-dependent helicase whose activity drives Aly loading onto RNA.

    Evidence In vitro ATPase, RNA helicase unwinding, and Aly-loading assays with helicase-motif mutagenesis and Xenopus export assay

    PMID:17562711 PMID:17984224

    Open questions at the time
    • Whether ATP hydrolysis versus binding suffices for export not fully separated here
    • In vivo substrate selectivity unaddressed
  6. 2010 High

    Demonstrated that TREX assembly is ATP-dependent and DDX39B bridges Aly and CIP29/SARNP, defining the architecture of the export-competent mRNP nucleator.

    Evidence Proteomics of immunopurified TREX and in vitro reconstitution with recombinant proteins

    PMID:20844015

    Open questions at the time
    • Stoichiometry of the complex not yet defined
    • How TREX engages the NPC unresolved
  7. 2010 High

    Distinguished DDX39B from its paralog by showing it nucleates the canonical TREX complex with distinct genome-wide targets and mitotic functions.

    Evidence Reciprocal Co-IP, siRNA depletion, genome-wide microarray, flow cytometry, and live-cell imaging

    PMID:20573985

    Open questions at the time
    • Structural determinants of paralog divergence not yet defined
    • Mechanism linking export to cohesion unclear
  8. 2020 High

    Revealed a genome-protective role: DDX39B is a cotranscriptional RNA-DNA helicase that unwinds R-loops to prevent transcription-replication conflicts.

    Evidence siRNA depletion, S9.6 R-loop detection, DNA fiber assays, in vitro RNA-DNA helicase assay, and ChIP-seq

    PMID:32439635

    Open questions at the time
    • Recruitment to specific R-loop-prone loci not fully mapped
    • Relationship between export and R-loop functions unresolved
  9. 2023 Medium

    Established substrate-specific splicing control: DDX39B promotes pre-spliceosome assembly on introns with C-rich/U-poor polypyrimidine tracts such as FOXP3.

    Evidence siRNA knockdown, in vitro commitment-complex assembly assays, polypyrimidine-tract mutagenesis, and Treg transcriptomics

    PMID:37261960 PMID:38575347 PMID:38801080

    Open questions at the time
    • How U2AF2 conformation gates DDX39B recruitment mechanistically incomplete
    • Generality across the transcriptome partially defined
  10. 2023 High

    Defined the multivalent SARNP-DDX39B mRNP architecture and its role in GC-rich mRNA export.

    Evidence X-ray crystallography of a Tho1/SARNP-DDX39B/RNA complex, Co-IP, and RNA-seq from knockdown

    PMID:37578863

    Open questions at the time
    • Functional consequence of variable DDX39B occupancy not resolved
    • Disassembly mechanism not defined here
  11. 2024 High

    Identified the nuclear machinery that releases DDX39B from mRNP, showing TREX-2 and a new TREX-2.1 complex control export of GC-rich transcripts via a conserved trigger loop.

    Evidence Cryo-EM of TREX-2/DDX39B and TREX-2.1/DDX39B complexes, Co-IP, knockdown, and RNA-seq

    PMID:40595470

    Open questions at the time
    • In vivo competition between release pathways not fully quantified
    • Trigger-loop catalytic mechanism partially defined
  12. 2025 Medium

    Connected DDX39B to human disease by showing de novo variants impair TREX interaction and cause developmental defects.

    Evidence In vitro Co-IP of variants, patient blood transcriptomics, and Drosophila/zebrafish models

    PMID:39918047

    Open questions at the time
    • Variant effects are partly variant-specific and complex
    • Tissue-specific disease mechanism not resolved
  13. 2025 Medium

    Expanded RNA fate control: DDX39B-bound RNA is interpreted by competing PAXT (decay) and TREX-2 (export) machineries, and DDX39B represses A-to-I editing by limiting dsRNA.

    Evidence Structural/mutagenesis and RNA-seq analyses (one preprint); CRISPR editing screen with knockdown follow-up

    PMID:40652511

    Open questions at the time
    • Determinants steering RNA toward decay versus export not fully defined
    • PAXT-competition model from preprint awaits peer review

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DDX39B's distinct functions—export, splicing, R-loop resolution, editing repression, and helicase-independent roles—are spatially and temporally partitioned within a single cell remains unresolved.
  • No integrated model coordinating multiple activities
  • Determinants of substrate and pathway choice undefined
  • In vivo regulation by PTMs across functions not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3 GO:0140657 ATP-dependent activity 3 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9609507 Protein localization 3 R-HSA-73894 DNA Repair 2
Partners
ALYREFDDX39ALENG8PCID2PLK1SARNP
Complex memberships
TREXTREX-2TREX-2.1

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 UAP56 directly and specifically interacts with the mRNA export factor Aly/REF, and is present together with Aly in the spliced mRNP. Excess UAP56 acts as a dominant negative inhibitor of mRNA export and blocks recruitment of Aly to the spliced mRNP. A mutation in Aly that blocks its interaction with UAP56 prevents recruitment of Aly to the spliced mRNP, demonstrating that UAP56 recruits Aly to couple splicing and mRNA export. Co-immunoprecipitation, dominant-negative overexpression, mutational analysis in Xenopus oocyte and mammalian systems Nature High 11675789
2001 The Drosophila UAP56 homolog HEL is essential for bulk mRNA export; depletion of HEL by RNAi causes nuclear accumulation of poly(A)+ RNA and inhibits global protein synthesis. Human UAP56 preferentially associates with spliced mRNAs carrying the exon junction complex in HeLa nuclear extracts. RNAi depletion in Drosophila Schneider cells, [35S]methionine incorporation, nuclear fractionation, co-immunoprecipitation Current biology : CB High 11696332
2001 UAP56/RAF-2p48/NPI-5/BAT1 interacts directly with influenza virus nucleoprotein (NP) via the amino-terminal RNA-binding domain of NP; UAP56 binds free NP but not RNA-bound NP, and facilitates NP-RNA complex formation, thereby enhancing influenza virus RNA synthesis. Yeast two-hybrid, in vitro binding assays, biochemical RNA synthesis assay with purified RAF-2 fraction Journal of virology Medium 11160689
2002 In Chironomus tentans, HEL/UAP56 binds cotranscriptionally to the Balbiani ring pre-mRNA independently of intron location, accompanies the mRNP to the nuclear pore, and is released from the mRNP during translocation to the cytoplasm, before Aly/REF dissociation. Immunoelectron microscopy, in situ analysis of mRNP at nuclear pore Current biology : CB Medium 12015125
2003 RNAi depletion of UAP56 in C. elegans causes strong nuclear retention of mRNA (suppression of GFP reporter expression due to nuclear retention), and overexpression of UAP56 also causes rapid loss of GFP expression and lethality, establishing UAP56 as a key mRNA export factor in worms. RNAi in C. elegans, GFP reporter assay, fluorescence microscopy RNA (New York, N.Y.) Medium 12810918
2004 Crystal structure of human UAP56 was solved, revealing a unique spatial arrangement of two RecA-like helicase domains. ADP binding induces significant conformational changes in the ATP-binding pocket. Purified UAP56 is an active RNA-dependent ATPase. Structural analyses suggest a protein-RNA displacement model for UAP56/Sub2 function. X-ray crystallography (crystal structures of UAP56 alone, ADP-bound, and DECD→DEAD mutant); in vitro ATPase assay Proceedings of the National Academy of Sciences of the United States of America High 15585580
2004 Crystal structures of the N- and C-terminal domains of human UAP56 at 1.9 Å resolution revealed two RecA-like domains connected by a flexible linker, similar to eIF4A, with an NTP binding pocket occupied by citrate. The N-terminal domain reveals a dimer interface potentially important for UAP56 function. X-ray crystallography Structure (London, England : 1993) High 15296731
2004 Both UAP56 and its paralog URH49 interact with the mRNA export factor Aly and both can rescue loss of Sub2p in yeast, indicating functionally overlapping roles in splicing and mRNA export. Yeast complementation assay, co-immunoprecipitation Nucleic acids research Medium 15047853
2006 Human cytomegalovirus pUL69 promotes cytoplasmic accumulation of unspliced RNA by directly interacting with UAP56 and URH49 via a 12-amino-acid N-terminal domain; both UAP56 interaction and nucleocytoplasmic shuttling of pUL69 are required for its mRNA export activity. Co-immunoprecipitation, deletion/mutation mapping, mRNA export assay Molecular and cellular biology Medium 16478985
2006 siRNA depletion of either UAP56 or URH49 alone in HeLa cells causes speckled nuclear accumulation of poly(A)+ RNA; combined depletion of both causes major reduction in reporter gene expression and cell death within 72 h, demonstrating essential but largely redundant functions in mRNA processing and export. siRNA knockdown, fluorescence in situ hybridization (FISH) for poly(A)+ RNA, reporter gene assay Gene Medium 16949217
2007 UAP56 promotes ATP-dependent loading of Aly/REF onto intronless mRNAs in vitro; ATP activates the RNA-binding activity of UAP56 itself, and ATP-bound UAP56 binds both RNA and Aly/REF simultaneously, stimulating UAP56's ATPase activity cooperatively. An ATP-binding-deficient UAP56 mutant specifically inhibits mRNA export in Xenopus oocytes. In vitro RNA binding assays, ATPase assays, Xenopus oocyte mRNA export assay with dominant-negative mutant Molecular and cellular biology High 17984224
2007 UAP56 is an RNA-stimulated ATPase that can only hydrolyze ATP (not other NTPs) and is an ATP-dependent RNA helicase capable of unwinding substrates with 5' or 3' overhangs or blunt ends. Mutations in conserved helicase motifs I, II, and III abolish ATPase and/or helicase activity. U2AF65 and Aly do not influence UAP56's ATPase or helicase activity. In vitro ATPase assay, RNA helicase unwinding assay, site-directed mutagenesis of helicase motifs The Journal of biological chemistry High 17562711
2007 UAP56 is required for bulk mRNA export from nurse cell nuclei in Drosophila, and also functions in the cytoplasm for remodeling RNP complexes that dictate cytoplasmic mRNA localization; loss of UAP56 disrupts localization of gurken, bicoid, and oskar mRNAs and post-translational modification of Osk protein. Drosophila genetics (loss-of-function alleles), RNA FISH, grk RNA injection into oocyte cytoplasm Developmental biology Medium 18237727
2008 ATP binding (but not hydrolysis per se) by UAP56 is required for mRNA export; a point mutant unable to bind ATP fails to export mRNA but does not affect RNA splicing. UAP56 is concentrated in nuclear speckle domains and in equilibrium binding at speckles regulated by ATP, as measured by FRAP. Confocal microscopy, FRAP, ATP-binding point mutant, mRNA export assay Journal of cell science Medium 18411249
2010 CIP29/SARNP was identified as a new component of the human TREX complex. UAP56 mediates an ATP-dependent interaction between the THO complex and both CIP29 and Aly. Using recombinant proteins, UAP56, Aly, and CIP29 form an ATP-dependent trimeric complex in which UAP56 bridges the CIP29–Aly interaction, establishing that TREX assembly is ATP-dependent. Proteomic analysis of immunopurified TREX, in vitro reconstitution with recombinant proteins from E. coli, ATP-dependence assays Genes & development High 20844015
2010 UAP56 and its paralog URH49 form distinct mRNA export complexes: UAP56 forms the canonical human TREX complex, while URH49 forms a distinct URH49-CIP29 complex (AREX). The two helicases regulate different genome-wide sets of mRNAs. Depletion of UAP56 causes mitotic delay and sister chromatid cohesion defects, while URH49 depletion causes chromosome arm resolution defects and cytokinesis failure. Co-immunoprecipitation, siRNA depletion, genome-wide microarray, flow cytometry, live-cell imaging Molecular biology of the cell High 20573985
2011 UAP56 is required to prevent accumulation of double-stranded RNA (dsRNA) during influenza A virus infection; siRNA depletion of UAP56 leads to rapid accumulation of dsRNA in the perinuclear region and robust activation of dsRNA-dependent PKR. UAP56 depletion also reduces nuclear export of M1 and HA viral mRNAs. siRNA knockdown, immunofluorescence for dsRNA, PKR activation assay, mRNA nuclear export assay Journal of virology Medium 21680511
2011 Interferon-induced antiviral protein MxA directly interacts with UAP56 and URH49 in vitro using purified recombinant proteins; MxA forms complexes with UAP56/URH49 in the perinuclear region of cells, and mouse Mx1 (nuclear) interacts with UAP56/URH49 in distinct nuclear dots. Co-immunoprecipitation, in vitro binding assay with purified recombinant proteins, immunofluorescence colocalization The Journal of biological chemistry Medium 21859714
2011 Polo-like kinase 1 (Plk1) interacts with UAP56 and phosphorylates it both in vitro and in vivo; Plk1-dependent phosphorylation of UAP56 triggers its ubiquitination and proteasomal degradation, inversely correlating UAP56 and Plk1 protein levels during the cell cycle. Co-immunoprecipitation, in vitro kinase assay, proteasome inhibitor treatment, cell cycle analysis Molecular biology reports Medium 21637952
2011 UAP56 exhibits a CRM1-independent nucleocytoplasmic shuttling activity; intranuclear localization requires UAP56 amino acids 81–381, REF interaction requires residues 51–428, and the shuttling activity maps to the C-terminus (aa 195–428). Human UAP56 shuttles independently of Rae1, unlike its S. pombe ortholog. Heterokaryon shuttling assay, deletion/truncation mutant mapping, co-immunoprecipitation PloS one Medium 21799930
2012 In Drosophila, UAP56 colocalizes with the piRNA cluster-associated HP1 variant Rhino in the nucleus; cluster transcripts immunoprecipitate with both UAP56 and Vasa. A charge-substitution mutation of a conserved surface residue in UAP56 disrupts colocalization with Rhino, germline piRNA production, transposon silencing, and perinuclear localization of Vasa, establishing UAP56 as a component of the nuclear phase of a piRNA processing compartment spanning the nuclear envelope. Immunofluorescence colocalization, RNA immunoprecipitation, piRNA sequencing, transposon silencing assay, UAP56 charge-substitution mutant analysis Cell High 23141543
2016 DDX39B (UAP56) directly binds FUT3 pre-mRNA and promotes its splicing and nuclear export in colorectal cancer cells; upregulation of FUT3 activates TGFβ signaling via fucosylation of TGFβR-I, driving EMT. RIP-seq, minigene splicing assay, nuclear/cytoplasmic RNA fractionation, RNA-seq, gain/loss-of-function assays Cell death & disease Medium 33436563
2016 shRNA screen identified DDX39B as a regulator of AR-V7 splice variant mRNA expression in prostate cancer; simultaneous knockdown of DDX39B and its paralog DDX39A drastically and selectively downregulated AR-V7 mRNA in multiple AR-V7-positive cell lines. shRNA library screen, siRNA knockdown, RT-PCR Biochemical and biophysical research communications Low 28025139
2017 UAP56 forms a complex with trimeric NP of influenza virus (not monomeric NP); two trimeric NP molecules are connected by UAP56 in the complex. UAP56 stimulates trimeric NP formation from monomeric NP and facilitates viral RNP formation by transferring trimeric NP to viral RNA, also preventing excess NP binding to RNA. Gel filtration, atomic force microscopy, co-immunoprecipitation, in vitro NP oligomerization assay Scientific reports Medium 29070793
2018 DDX39B overexpression promotes global translation by upregulating pre-ribosomal RNA levels, regulating both the stability and synthesis of pre-rRNA. Overexpression, ribosomal RNA stability assays, translation assays RNA biology Low 30176153
2020 UAP56/DDX39B is a cotranscriptional RNA-DNA helicase that unwinds R loops genome-wide; its depletion causes R-loop accumulation, R-loop-mediated genome instability, and replication fork stalling. Overexpression of UAP56 suppresses R loops and genome instability induced by depletion of five different unrelated factors. UAP56 localizes to active chromatin. siRNA depletion, R-loop detection (S9.6 antibody), DNA damage assays, replication fork assay (DNA fiber), RNA-DNA helicase activity assay in vitro, ChIP-seq Genes & development High 32439635
2020 DDX39B inhibits NF-κB activity by inhibiting p65 phosphorylation; mechanistically, DDX39B interacts with the pattern recognition receptor LGP2 in a pathway requiring cellular response to cytoplasmic dsRNA. DDX39B protein abundance is regulated by site-specific sumoylation (mediated by SUMO E3 ligase PIASx-β) that promotes its poly-ubiquitination and degradation. Streptavidin-agarose pull-down with κB DNA probes, RNAi, CRISPR/Cas9, NF-κB reporter assay, Co-IP for LGP2 interaction, sumoylation and ubiquitination assays BMC biology Medium 32209106
2020 DDX39B binds to and stabilizes BRCA1 mRNA; DDX39B depletion reduces BRCA1 levels, impairs ssDNA formation and RAD51 accumulation at DSBs, and sensitizes ovarian cancer cells to platinum/PARPi. DDX39B-deficient mice show embryonic lethality reminiscent of BRCA1 knockout. RIP (RNA immunoprecipitation), siRNA knockdown, CRISPR knockout, DNA repair assays (RPA/RAD51 foci), mRNA stability assay Oncogene Medium 32989256
2020 UAP56 interacts with influenza A virus NP at two sites: the canonical UAP56 core (two RecA domains) and a previously unidentified N-terminal extension (NTE); the NTE recognizes the nucleic acid binding region of NP and binding of UAP56-NTE and RNA to NP is mutually exclusive. In vitro binding assays with recombinant proteins, domain mapping, competition binding assays Biochemical and biophysical research communications Medium 32085897
2022 DDX39B directly binds the first exon of CDK6 and CCND1 pre-mRNAs (confirmed by RIP-seq) and promotes their splicing; CDK6/CCND1 are downstream effectors mediating DDX39B-driven G1/S cell cycle progression in colorectal cancer cells. RIP-seq, minigene splicing assay (RT-PCR/gel electrophoresis), flow cytometry, rescue experiments Cell death discovery Medium 35046400
2022 RETSAT interacts with DDX39B at replication forks; RETSAT detains DDX39B on forks to resolve R-loops via DDX39B's helicase activity, preventing fork damage and CHK1-initiated apoptosis. iPOND combined with mass spectrometry, co-immunoprecipitation, DNA fiber assay Journal of experimental & clinical cancer research : CR Low 36109793
2023 Crystal structure of a Tho1/SARNP–DDX39B/RNA complex was determined, revealing that SARNP/Tho1 engages DDX39B through tandem DDX39B-interacting motifs forming a high-order multivalent complex. Human SARNP can engage up to five DDX39B molecules. The SARNP/DDX39B/RNA high-order complex is evolutionarily conserved and affects export of GC-rich mRNAs. X-ray crystallography, co-immunoprecipitation, RNA-seq from SARNP knockdown cells Cell reports High 37578863
2023 DDX39B controls FOXP3 pre-mRNA splicing; DDX39B knockdown leads to loss of immune-regulatory and gain of immune-effector expression signatures. FOXP3 introns have C-rich/U-poor polypyrimidine tracts that confer exquisite sensitivity to DDX39B levels. siRNA knockdown, splicing assays, transcriptomics (RNA-seq), T regulatory cell functional assays eLife Medium 37261960
2023 DDX39B directly interacts with SREBP1 protein; DDX39B deficiency promotes FBXW7-mediated ubiquitination and degradation of SREBP1, reducing SREBP1 nuclear translocation and activation, resulting in decreased lipid accumulation in hepatocellular carcinoma cells. Co-immunoprecipitation, immunofluorescence for nuclear translocation, luciferase transcriptional activity assay, ubiquitination assay Cellular oncology (Dordrecht, Netherlands) Low 37052853
2024 Cryo-EM structures of TREX-2.1/DDX39B and TREX-2/DDX39B complexes were determined. A novel nuclear complex TREX-2.1 (LENG8, PCID2, DSS1) was identified that facilitates release of DDX39B from mRNP; TREX-2.1 and TREX-2 share a conserved 'trigger loop' in LENG8 and GANP subunits respectively that is critical for DDX39B regulation. LENG8 knockdown alters nucleocytoplasmic ratio of GC-rich mRNAs. Cryo-EM structure determination, co-immunoprecipitation, siRNA knockdown, RNA-seq Nature communications High 40595470
2024 DDX39B promotes FOXP3 intron splicing at the pre-spliceosome assembly step; FOXP3 introns have C-rich/U-poor polypyrimidine tracts that reduce U2AF2 affinity and alter U2AF2 conformation, causing deficient recruitment of DDX39B to commitment complexes and inefficient CC-to-pre-spliceosome conversion. In vitro splicing/commitment complex assembly assays, RNA-protein binding assays, mutagenesis of polypyrimidine tracts RNA (New York, N.Y.) Medium 38575347
2024 DDX39A and DDX39B have significant redundancy in splicing targets but also unique targets; DDX39A cannot complement DDX39B-dependent splicing of IL7R exon 6. Cassette exons uniquely dependent on DDX39B have U-poor/C-rich polypyrimidine tracts in the upstream intron, which is required for DDX39B dependency. siRNA knockdown, RNA-seq, minigene splicing assay, polypyrimidine tract mutagenesis Nucleic acids research Medium 38801080
2024 The structural basis of functional divergence between UAP56 and URH49 was established by comparing crystal structures and chimeric mutant analysis; unique structural features at the terminal regions of each helicase contribute to formation of distinct apo-TREX and apo-AREX complexes. Additional apo-AREX components physically and functionally associated with URH49 were identified. X-ray crystallography (UAP56 and URH49 structures), chimeric mutant analysis, co-immunoprecipitation Nature communications High 38225262
2024 DDX39B directly binds GPX4 pre-mRNA and promotes its splicing and cytoplasmic export; inhibition of DDX39B ATPase activity by CCT018159 represses GPX4 pre-mRNA splicing and export, sensitizing HCC cells to sorafenib-induced ferroptosis. RIP, nuclear/cytoplasmic fractionation, chemical inhibitor (CCT018159) of ATPase activity, splicing assay Biochemical pharmacology Medium 38701867
2024 The terminal regions of UAP56 are indispensable for TREX complex formation; a specific C-terminal amino acid of UAP56 is critical for complex formation, and its alanine substitution impairs complex formation and subsequently mRNA processing and export activity. Co-immunoprecipitation with deletion mutants, alanine substitution mutagenesis, mRNA export assay Biochemical and biophysical research communications Low 38377942
2025 De novo missense variants in DDX39B (e.g., p.Gly92Asp) and a splicing variant (c.433-1G>T) impair interaction with other TREX complex members in vitro; patient blood transcriptomics shows elevated aberrant splicing events; Drosophila and zebrafish models confirm loss-of-function effects on development. In vitro overexpression Co-IP for TREX interaction, blood transcriptomics, Drosophila transgenic overexpression lethality assay, zebrafish morpholino knockdown with mRNA rescue Brain : a journal of neurology Medium 39918047
2025 DDX39B undergoes TRIM28-mediated K63-linked ubiquitination at Lys241, Lys384, and Lys398 via interaction through Pro322; this ubiquitination stabilizes DDX39B protein. Stabilized DDX39B directly binds ECAD and promotes its lysosomal degradation by recruiting Src and Hakai, independent of DDX39B's RNA helicase activity, activating β-catenin signaling. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, immunofluorescence, functional metastasis assays Signal transduction and targeted therapy Medium 40664668
2025 DDX39B functions as a global repressor of A-to-I RNA editing by preventing double-stranded RNA accumulation through its helicase activity; DDX39B depletion significantly enhances A-to-I RNA editing efficiency genome-wide. CRISPR-based genetic screen (CREDITS/scCREDIT-seq), RNA editing transcriptomics, mechanistic follow-up with DDX39B knockdown Cell reports Medium 40652511
2025 The PAXT complex harbors a TREX-2-like LENG8-PCID2-SEM1 (LENG8-PS) module structurally and functionally equivalent to the GANP-PCID2-SEM1 trimer of TREX-2; this module releases pA+ RNAs from UAP56 for nuclear exosome-mediated decay. The nuclear fate of pA+ RNPs is governed by competition between nucleoplasmic PAXT and NPC-associated TREX-2, both interpreting RNA-bound UAP56 as a signal for either RNA decay or export, respectively. Structural analysis (cryo-EM/mutagenesis), RNA-seq, interaction/pulldown assays bioRxivpreprint Medium bio_10.1101_2025.09.16.676470
2026 Loss of UAP56 in Drosophila c4da sensory neurons causes dendrite and presynapse pruning defects during metamorphosis; this is linked to impaired ecdysone-induced expression of the actin-severing enzyme Mical and to actin accumulation at pruning presynapses, demonstrating a role for UAP56-dependent mRNA export in actin regulation during neuronal remodeling. Drosophila genetics (loss-of-function), immunofluorescence, live imaging, mRNA expression analysis Journal of cell science Medium 41958408

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 331 11675789
2001 The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Current biology : CB 199 11696332
2012 UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 186 23141543
2010 ATP is required for interactions between UAP56 and two conserved mRNA export proteins, Aly and CIP29, to assemble the TREX complex. Genes & development 148 20844015
2001 Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis. Journal of virology 144 11160689
2020 UAP56/DDX39B is a major cotranscriptional RNA-DNA helicase that unwinds harmful R loops genome-wide. Genes & development 112 32439635
2004 Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proceedings of the National Academy of Sciences of the United States of America 105 15585580
2006 The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA. Molecular and cellular biology 102 16478985
2007 ATP-dependent recruitment of export factor Aly/REF onto intronless mRNAs by RNA helicase UAP56. Molecular and cellular biology 98 17984224
2010 The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression. Molecular biology of the cell 87 20573985
2007 Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. The Journal of biological chemistry 83 17562711
2003 UAP56 levels affect viability and mRNA export in Caenorhabditis elegans. RNA (New York, N.Y.) 78 12810918
2004 Growth-regulated expression and G0-specific turnover of the mRNA that encodes URH49, a mammalian DExH/D box protein that is highly related to the mRNA export protein UAP56. Nucleic acids research 66 15047853
2006 Nuclear localization of poly(A)+ mRNA following siRNA reduction of expression of the mammalian RNA helicases UAP56 and URH49. Gene 63 16949217
2011 The cellular RNA helicase UAP56 is required for prevention of double-stranded RNA formation during influenza A virus infection. Journal of virology 61 21680511
2004 Crystal structure of UAP56, a DExD/H-box protein involved in pre-mRNA splicing and mRNA export. Structure (London, England : 1993) 59 15296731
2021 The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer. Cell death & disease 55 33436563
2008 Binding of ATP to UAP56 is necessary for mRNA export. Journal of cell science 55 18411249
2002 HEL/UAP56 binds cotranscriptionally to the Balbiani ring pre-mRNA in an intron-independent manner and accompanies the BR mRNP to the nuclear pore. Current biology : CB 54 12015125
2009 UAP56- a key player with surprisingly diverse roles in pre-mRNA splicing and nuclear export. BMB reports 52 19403039
2016 The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation. Biochemical and biophysical research communications 51 28025139
2020 Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA. Oncogene 39 32989256
2007 UAP56 RNA helicase is required for axis specification and cytoplasmic mRNA localization in Drosophila. Developmental biology 36 18237727
2011 Interferon-induced antiviral protein MxA interacts with the cellular RNA helicases UAP56 and URH49. The Journal of biological chemistry 35 21859714
2022 DDX39B contributes to the proliferation of colorectal cancer through direct binding to CDK6/CCND1. Cell death discovery 31 35046400
2014 DDX39B (BAT1), TNF and IL6 gene polymorphisms and association with clinical outcomes of patients with Plasmodium vivax malaria. Malaria journal 27 25038626
2008 Isolation and characterization of Plasmodium falciparum UAP56 homolog: evidence for the coupling of RNA binding and splicing activity by site-directed mutations. Archives of biochemistry and biophysics 27 18722339
2023 The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate. eLife 26 37261960
2023 DDX39B facilitates the malignant progression of hepatocellular carcinoma via activation of SREBP1-mediated de novo lipid synthesis. Cellular oncology (Dordrecht, Netherlands) 25 37052853
2010 UAP56 is an important regulator of protein synthesis and growth in cardiomyocytes. Biochemical and biophysical research communications 25 20116367
2020 DDX39B interacts with the pattern recognition receptor pathway to inhibit NF-κB and sensitize to alkylating chemotherapy. BMC biology 24 32209106
2018 DDX39B promotes translation through regulation of pre-ribosomal RNA levels. RNA biology 24 30176153
2011 The cellular DExD/H-box RNA-helicases UAP56 and URH49 exhibit a CRM1-independent nucleocytoplasmic shuttling activity. PloS one 22 21799930
2016 UAP56 is a conserved crucial component of a divergent mRNA export pathway in Toxoplasma gondii. Molecular microbiology 19 27542978
2023 Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly. Cell reports 17 37578863
2010 Characterization of the betaherpesviral pUL69 protein family reveals binding of the cellular mRNA export factor UAP56 as a prerequisite for stimulation of nuclear mRNA export and for efficient viral replication. Journal of virology 16 21147923
2022 RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma. Journal of experimental & clinical cancer research : CR 15 36109793
2025 Structural mechanism of DDX39B regulation by human TREX-2 and a related complex in mRNP remodeling. Nature communications 14 40595470
2020 Cellular mRNA export factor UAP56 recognizes nucleic acid binding site of influenza virus NP protein. Biochemical and biophysical research communications 14 32085897
2024 Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing. Nucleic acids research 13 38801080
2024 Structural differences between the closely related RNA helicases, UAP56 and URH49, fashion distinct functional apo-complexes. Nature communications 12 38225262
2024 Critical Cellular Functions and Mechanisms of Action of the RNA Helicase UAP56. Journal of molecular biology 12 38729260
2020 Phosphosite Analysis of the Cytomegaloviral mRNA Export Factor pUL69 Reveals Serines with Critical Importance for Recruitment of Cellular Proteins Pin1 and UAP56/URH49. Journal of virology 12 31969433
2020 Cellular UAP56 interacts with the HBx protein of the hepatitis B virus and is involved in viral RNA nuclear export in hepatocytes. Experimental cell research 12 32169426
2011 Plk1-mediated phosphorylation of UAP56 regulates the stability of UAP56. Molecular biology reports 12 21637952
2010 Requirement of UAP56, URH49, RBM15, and OTT3 in the expression of Kaposi sarcoma-associated herpesvirus ORF57. Virology 12 20828777
2009 Uncoupling of hTREX demonstrates that UAP56 and hTHO-complex recruitment onto herpesvirus saimiri intronless transcripts is required for replication. The Journal of general virology 12 19264631
2019 The UAP56-Interacting Export Factors UIEF1 and UIEF2 Function in mRNA Export. Plant physiology 11 30700540
2018 The Cellular DExD/H-Box RNA Helicase UAP56 Co-localizes With the Influenza A Virus NS1 Protein. Frontiers in microbiology 11 30258431
2017 Cellular splicing factor UAP56 stimulates trimeric NP formation for assembly of functional influenza viral ribonucleoprotein complexes. Scientific reports 11 29070793
2024 DDX39B protects against sorafenib-induced ferroptosis by facilitating the splicing and cytoplasmic export of GPX4 pre-mRNA in hepatocellular carcinoma. Biochemical pharmacology 9 38701867
2010 Binding of the human cytomegalovirus (HCMV) tegument protein UL69 to UAP56/URH49 is not required for efficient replication of HCMV. Journal of virology 9 20610707
2025 De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome. Brain : a journal of neurology 7 39918047
2025 DDX39B K63-linked ubiquitination mediated by TRIM28 promotes NSCLC metastasis by enhancing ECAD lysosomal degradation. Signal transduction and targeted therapy 7 40664668
2012 Transfer of the UAP56 interaction motif of human cytomegalovirus pUL69 to its murine cytomegalovirus homolog converts the protein into a functional mRNA export factor that can substitute for pUL69 during viral infection. Journal of virology 6 22553320
2023 Valine promotes milk synthesis by regulating PKM2 nuclear accumulation and histone H3 acetylation through the TAS1R1-mTOR-DDX39B signaling pathway. International journal of biological macromolecules 5 37918588
2017 Heat shock factor 4 regulates the expression of HSP25 and alpha B-crystallin by associating with DEXD/H-box RNA helicase UAP56. Cell stress & chaperones 5 29164525
2012 UAP56 is a novel interacting partner of Bcr in regulating vascular smooth muscle cell DNA synthesis. Biochemical and biophysical research communications 5 22446327
2012 UAP56 is an important mediator of angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation. Biochemical and biophysical research communications 5 23246467
2025 Multimodal CRISPR screens uncover DDX39B as a global repressor of A-to-I RNA editing. Cell reports 3 40652511
2024 Inefficient recruitment of DDX39B impedes pre-spliceosome assembly on FOXP3 introns. RNA (New York, N.Y.) 3 38575347
2012 Capturing the cloud: UAP56 in nuage assembly and function. Cell 3 23141532
2025 The RNA-binding protein DDX39B promotes colorectal adenocarcinoma progression by stabilizing DCLK1. Human molecular genetics 2 40583564
2024 Terminal regions of UAP56 and URH49 are required for their distinct complex formation functioning to an essential role in mRNA processing and export. Biochemical and biophysical research communications 1 38377942
2026 HSF1-dependent, long-range directional HSPA1 gene motion to nuclear speckles is coupled to DDX39B condensate dynamics. bioRxiv : the preprint server for biology 0 41542407
2026 SNRPD2-mediated regulation of DDX39B splicing promotes endometrial cancer progression by suppressing the activation of CTSC cryptic exons. Cell death & disease 0 41720762
2026 Screening for influenza B virus NS1-interacting host proteins and characterization of interactions with hnRNPA0 and DDX39B. Virus genes 0 41817792
2026 The mRNA export factor UAP56 is required for dendrite and synapse pruning via actin regulation in Drosophila. Journal of cell science 0 41958408
2025 Baculovirus 25K hijacks host UAP56 to facilitate nuclear export of viral mRNA in insect cells. Journal of virology 0 40985718
2025 Cellular hnRNP AB inhibits avian influenza virus RNA synthesis via blocking UAP56-mediated nuclear export of PB2 mRNA. Veterinary research 0 41272896

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