Affinage

DDX39B

Spliceosome RNA helicase DDX39B · UniProt Q13838

Length
428 aa
Mass
49.0 kDa
Annotated
2026-04-28
99 papers in source corpus 38 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX39B (UAP56) is an essential ATP-dependent DEAD-box RNA helicase that functions as a central hub connecting pre-mRNA splicing, mRNA nuclear export, R-loop resolution, and genome stability maintenance. It cotranscriptionally loads onto nascent pre-mRNPs, uses ATP binding and hydrolysis to chaperone the export adaptor Aly/REF onto mRNAs, and bridges THO complex–Aly–CIP29 interactions to assemble the TREX complex required for bulk mRNA export (PMID:11675789, PMID:20844015, PMID:12015125). DDX39B specifically promotes pre-spliceosome (A-complex) formation on introns bearing C-rich/U-poor polypyrimidine tracts—including those in FOXP3 and IL7R—by collaborating with U2AF2, and its depletion globally impairs splicing of these transcripts; additionally, its RNA-DNA helicase activity resolves co-transcriptional R-loops genome-wide, preventing R-loop-mediated replication stress and DNA damage (PMID:38575347, PMID:37261960, PMID:32439635). Loss-of-function missense and splice-site variants in DDX39B cause a neurodevelopmental syndrome characterized by impaired TREX complex assembly and aberrant splicing (PMID:39918047).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Establishing DDX39B as the adaptor-loading machine for mRNA export resolved how splicing and export are coupled: UAP56 directly recruits Aly/REF to spliced mRNPs, and dominant-negative UAP56 blocks both Aly recruitment and mRNA export.

    Evidence Co-immunoprecipitation, dominant-negative overexpression in HeLa nuclear extracts, separation-of-function Aly mutant; RNAi in Drosophila S2 cells with poly(A)+ FISH

    PMID:11675789 PMID:11696332

    Open questions at the time
    • Mechanism of UAP56 recruitment to mRNP not yet defined
    • Whether ATP hydrolysis is needed for Aly loading was unknown
  2. 2004 High

    Crystal structures of UAP56 revealed two RecA-like helicase domains and showed ADP-induced conformational changes, providing the first structural framework for understanding its chaperone mechanism.

    Evidence X-ray crystallography of apo and ADP-bound UAP56 at 1.9 Å resolution; in vitro ATPase assay

    PMID:15296731 PMID:15585580

    Open questions at the time
    • No structure with RNA or protein partner bound
    • Whether dimerization observed crystallographically is functionally relevant remained unclear
  3. 2007 High

    Dissection of the ATP cycle showed that ATP-bound UAP56 simultaneously engages RNA and Aly/REF, with ATP hydrolysis triggering UAP56 dissociation after Aly deposition—establishing UAP56 as an ATP-driven chaperone rather than a processive helicase for export adaptor loading.

    Evidence In vitro RNA-binding and Aly-loading assays with ATP analogues; Xenopus oocyte mRNA export with ATP-binding mutant; in vitro helicase unwinding assays with motif mutants

    PMID:17562711 PMID:17984224

    Open questions at the time
    • How UAP56 selects specific mRNPs was unknown
    • Structural basis of simultaneous RNA and Aly binding not resolved
  4. 2010 High

    Reconstitution of the human TREX complex showed UAP56 bridges THO–Aly–CIP29 in an ATP-dependent manner, and depletion revealed UAP56-specific (versus URH49-specific) mRNA targets and mitotic phenotypes, establishing paralog-specific export pathways.

    Evidence Recombinant protein reconstitution, immunopurification/MS proteomics; siRNA depletion with genome-wide mRNA profiling and mitotic phenotype analysis

    PMID:20573985 PMID:20844015

    Open questions at the time
    • Structural basis of paralog specificity not defined
    • How UAP56 vs URH49 select distinct mRNA subsets was unknown
  5. 2012 High

    In Drosophila, UAP56 was shown to function at piRNA cluster loci with the heterochromatin protein Rhino, linking its RNA handling activity to transposon silencing and germline genome defense beyond canonical mRNA export.

    Evidence Immunofluorescence co-localization, RNA immunoprecipitation of piRNA cluster transcripts, charge-substitution mutagenesis disrupting Rhino interaction and piRNA production

    PMID:23141543

    Open questions at the time
    • Whether this piRNA function is conserved in mammals
    • Direct enzymatic activity on piRNA precursors not demonstrated
  6. 2020 High

    DDX39B was established as a cotranscriptional RNA-DNA helicase that resolves R-loops genome-wide; its overexpression rescues R-loop accumulation caused by depletion of five unrelated factors, positioning DDX39B as a general guardian of genome stability.

    Evidence In vitro RNA-DNA helicase assay, DRIP-seq, DNA damage markers, replication fork assays, overexpression rescue

    PMID:32439635

    Open questions at the time
    • How DDX39B is recruited to R-loop sites versus mRNP export sites not resolved
    • Relative contribution of R-loop resolution versus mRNA export to genome stability phenotype unclear
  7. 2020 Medium

    DDX39B was linked to innate immune regulation: it inhibits NF-κB via interaction with LGP2, and its protein abundance is controlled by PIASx-β sumoylation promoting poly-ubiquitination and degradation, revealing post-translational regulatory layers.

    Evidence CRISPR KO, Co-IP with LGP2, p65 phosphorylation assays, sumoylation/ubiquitination assays in multiple cell types

    PMID:32209106

    Open questions at the time
    • NF-κB inhibition mechanism downstream of LGP2 interaction not fully elucidated
    • Whether sumoylation-mediated degradation is the dominant regulatory mode in vivo unclear
  8. 2023 High

    The discovery that DDX39B specifically controls splicing of introns with C-rich/U-poor polypyrimidine tracts—including FOXP3 and other MS susceptibility genes—revealed a non-redundant splicing function distinct from its paralog DDX39A and linked DDX39B to immune homeostasis.

    Evidence siRNA knockdown with RT-PCR splicing assays and transcriptomic profiling in human T cells; crystal structure of SARNP/DDX39B/RNA complex

    PMID:37261960 PMID:37578863

    Open questions at the time
    • Whether DDX39B directly contacts the C-rich polypyrimidine tract or acts through U2AF2 remodeling was unresolved
    • Full scope of immune-relevant DDX39B-dependent splicing events not catalogued
  9. 2024 High

    Mechanistic dissection showed that C-rich polypyrimidine tracts adopt an altered U2AF2 conformation with reduced DDX39B affinity, explaining how DDX39B protein levels gate commitment-to-A-complex conversion on specific introns—a rate-limiting step in selective splicing.

    Evidence In vitro spliceosome assembly assays, U2AF2 binding assays; minigene mutagenesis of polypyrimidine tracts

    PMID:38575347 PMID:38801080

    Open questions at the time
    • Structural basis of the altered U2AF2–DDX39B interface on C-rich tracts not determined
    • Whether additional cofactors modulate this selectivity in vivo
  10. 2024 High

    Cryo-EM structures of TREX-2/DDX39B complexes revealed a conserved trigger loop in GANP that controls DDX39B release from mRNPs at the nuclear pore, and identified LENG8 (TREX-2.1) as an alternative release factor preferentially affecting GC-rich mRNA export; chimeric analyses defined terminal regions of UAP56 dictating TREX versus AREX complex specificity.

    Evidence Cryo-EM and X-ray crystallography, trigger-loop mutagenesis, RNA-seq from LENG8 KD; chimeric UAP56/URH49 mutants with Co-IP

    PMID:38225262 PMID:40595470

    Open questions at the time
    • How TREX-2 versus PAXT pathway competition is regulated in different cell types
    • Whether the trigger loop mechanism is conserved in non-mammalian TREX-2
  11. 2025 High

    Human genetics established DDX39B loss-of-function as causal for a neurodevelopmental syndrome: patient missense variants impair TREX complex assembly or cause aberrant splicing, and zebrafish knockdown recapitulates developmental defects rescued by DDX39B mRNA.

    Evidence In vitro Co-IP with patient variants, blood transcriptomics, zebrafish morpholino knockdown with mRNA rescue, Drosophila transgenic assays

    PMID:39918047

    Open questions at the time
    • Genotype-phenotype correlations across the variant spectrum not fully defined
    • Which DDX39B-dependent splicing events are most critical for neurodevelopment unknown
  12. 2025 Medium

    DDX39B was identified as a global repressor of A-to-I RNA editing: its helicase activity prevents dsRNA accumulation that would otherwise serve as ADAR substrates, expanding its role in RNA structure surveillance beyond R-loop resolution.

    Evidence Genome-scale CRISPR screen, single-cell CRISPR RNA-seq, transcriptome-wide A-to-I editing profiling

    PMID:40652511

    Open questions at the time
    • Whether DDX39B acts directly on ADAR substrates or indirectly via global dsRNA levels
    • Relationship between editing suppression and innate immune dsRNA sensing not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for how DDX39B discriminates between R-loops, dsRNA, and mRNP substrates; how the TREX-2 versus PAXT competition is regulated to determine RNA fate; and which DDX39B-dependent splicing events are most critical for neurodevelopment and immune regulation.
  • No structure of DDX39B bound simultaneously to R-loop substrate and regulatory partners
  • Mechanism governing DDX39B allocation between splicing, export, and R-loop resolution functions unknown
  • Tissue-specific consequences of DDX39B haploinsufficiency not systematically characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140657 ATP-dependent activity 5 GO:0044183 protein folding chaperone 4 GO:0140098 catalytic activity, acting on RNA 2 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-9609507 Protein localization 7 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 2
Partners
ALYREFGANPLENG8LGP2MXASARNPTHOC1U2AF2
Complex memberships
TREXTREX-2

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 UAP56 directly interacts with the mRNA export adaptor Aly/REF, and this interaction recruits Aly to the spliced mRNP, coupling pre-mRNA splicing to mRNA export. Excess UAP56 acts as a dominant-negative inhibitor of mRNA export and blocks Aly recruitment to the spliced mRNP. Co-immunoprecipitation, dominant-negative overexpression in HeLa nuclear extracts, Aly mutation that blocks UAP56 interaction prevents Aly recruitment to spliced mRNP Nature High 11675789
2001 Drosophila HEL (UAP56 ortholog) is essential for bulk mRNA nuclear export; depletion causes nuclear accumulation of poly(A)+ RNA and inhibits protein synthesis from both spliced and intronless mRNAs. RNAi depletion in Drosophila Schneider cells, fluorescence in situ hybridization for poly(A)+ RNA, [35S]methionine incorporation assay Current Biology High 11696332
2001 UAP56 (RAF-2p48/BAT1) is a cellular splicing factor that interacts directly with influenza virus nucleoprotein (NP); it binds RNA-free NP but not RNA-bound NP, and facilitates NP-RNA complex formation required for viral RNA synthesis. Yeast two-hybrid, in vitro binding assays with purified proteins, influenza RNA synthesis reconstitution assay Journal of Virology High 11160689
2004 Crystal structure of human UAP56 reveals two RecA-like helicase domains connected by a flexible linker; ADP binding induces significant conformational changes in the ATP-binding pocket. Purified UAP56 is an active RNA-dependent ATPase. Structure suggests a protein-RNA displacement model for UAP56/Sub2 function. X-ray crystallography of UAP56 alone, UAP56-ADP complex, and DECD→DEAD mutant; in vitro ATPase assay Proceedings of the National Academy of Sciences High 15585580
2004 Crystal structures of the N- and C-terminal domains of human UAP56 at 1.9 Å resolution reveal RecA-like folds similar to eIF4A; the N-terminal domain shows a dimer interface potentially important for UAP56 function. The NTP-binding pocket contains a citrate ion mimicking phosphates, retaining the P-loop in open conformation. X-ray crystallography Structure High 15296731
2006 Human cytomegalovirus pUL69 interacts directly with UAP56 and URH49 via a 12-amino-acid N-terminal domain, and this interaction plus nucleocytoplasmic shuttling are both required for pUL69-mediated nuclear export of unspliced viral mRNA. Co-immunoprecipitation, domain mapping, heterokaryon shuttling assay, mRNA export reporter assay Molecular and Cellular Biology High 16478985
2007 UAP56 promotes ATP-dependent loading of Aly/REF onto intronless mRNAs in vitro. ATP-bound UAP56 binds both RNA and Aly/REF simultaneously, and ATP hydrolysis drives UAP56 dissociation after Aly loading. An ATP-binding-deficient UAP56 mutant specifically inhibits mRNA export in Xenopus oocytes. In vitro RNA-binding assay, ATP analogue experiments, Xenopus oocyte mRNA export assay with dominant-negative mutant Molecular and Cellular Biology High 17984224
2007 UAP56 is an RNA-stimulated ATPase that specifically hydrolyzes ATP 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. In vitro ATPase assay, in vitro helicase unwinding assay, site-directed mutagenesis of conserved motifs Journal of Biological Chemistry High 17562711
2008 ATP binding by UAP56 is required for mRNA export but not for RNA splicing. UAP56 localizes to nuclear splicing speckle domains and is in dynamic equilibrium in complexes containing SRm160, as measured by FRAP; ATP binding regulates this equilibrium. Confocal microscopy, FRAP (live cells and in vitro digitonin-extracted cells), ATP-binding-deficient point mutant, mRNA export assay Journal of Cell Science High 18411249
2010 UAP56 mediates ATP-dependent interactions between the THO complex and both CIP29 and Aly to assemble the human TREX complex. Using recombinant proteins, UAP56, Aly, and CIP29 form an ATP-dependent trimeric complex in which UAP56 bridges CIP29 and Aly interactions. Proteomics (immunopurification/MS), recombinant protein reconstitution in E. coli, ATP-dependency biochemical assays Genes & Development High 20844015
2010 UAP56 forms the human TREX complex (distinct from URH49-containing AREX complex), and its depletion causes mitotic delay and sister chromatid cohesion defects; genome-wide analysis shows UAP56 and URH49 regulate distinct sets of target mRNAs including different mitotic regulators. siRNA depletion, immunofluorescence, mitotic phenotype analysis, genome-wide mRNA profiling Molecular Biology of the Cell High 20573985
2011 UAP56 depletion in influenza A virus-infected cells leads to rapid accumulation of double-stranded RNA (dsRNA) in the perinuclear region and robust activation of PKR, suggesting UAP56 is recruited by influenza virus to prevent dsRNA formation and thereby suppress innate immune activation. siRNA depletion, immunofluorescence for dsRNA, PKR activation assay, actinomycin D and cycloheximide controls Journal of Virology High 21680511
2011 Interferon-induced antiviral GTPase MxA directly binds UAP56 and URH49 in vitro and forms complexes with them in the perinuclear region in cells; mouse Mx1 also binds UAP56/URH49 in distinct nuclear dots. Immunoprecipitation, in vitro binding assay with purified recombinant proteins, immunofluorescence co-localization Journal of Biological Chemistry High 21859714
2011 UAP56 undergoes CRM1-independent nucleocytoplasmic shuttling; the intranuclear localization domain maps to aa81-381 and the shuttling domain maps to the C-terminus (aa195-428), which also mediates REF interaction. Shuttling is independent of Rae1 in human cells. Heterokaryon assay, deletion mapping with truncation mutants, immunofluorescence PLoS One Medium 21799930
2011 Polo-like kinase 1 (Plk1) physically interacts with UAP56, phosphorylates it in vitro and in vivo, and this phosphorylation triggers ubiquitination and proteasomal degradation of UAP56, inversely correlating protein levels of UAP56 and Plk1 during the cell cycle. Co-immunoprecipitation, in vitro kinase assay, in vivo phosphorylation, ubiquitination assay, proteasome inhibitor treatment Molecular Biology Reports Medium 21637952
2012 In Drosophila, nuclear UAP56 colocalizes with the heterochromatin protein HP1 variant Rhino at piRNA cluster loci; cluster transcripts immunoprecipitate with both UAP56 and Vasa; a charge-substitution mutation in UAP56 disrupts Rhino colocalization, germline piRNA production, transposon silencing, and perinuclear Vasa localization, placing UAP56 at the nuclear side of a piRNA-processing compartment spanning the nuclear envelope. Immunofluorescence, RNA immunoprecipitation, charge-substitution mutagenesis, piRNA sequencing Cell High 23141543
2012 UAP56 interacts with Bcr kinase; knockdown of UAP56 blocks Bcr-induced DNA synthesis and reverses Bcr-mediated upregulation of cyclin E and downregulation of p27 in vascular smooth muscle cells. Co-immunoprecipitation, siRNA knockdown, DNA synthesis assay, cyclin E/p27 western blot Biochemical and Biophysical Research Communications Low 22446327
2016 DDX39B (and its paralog DDX39A) regulate the generation of androgen receptor splice variant AR-V7; simultaneous knockdown of both DDX39B and DDX39A drastically and selectively downregulated AR-V7 mRNA expression in multiple prostate cancer cell lines. shRNA screen of spliceosome-related genes, siRNA knockdown of DDX39B and DDX39A in multiple cell lines, RT-PCR quantification of AR-V7 Biochemical and Biophysical Research Communications Medium 28025139
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. UAP56 overexpression suppresses R loops and genome instability induced by depletion of five unrelated factors. RNA-DNA helicase activity was demonstrated in vitro. In vitro RNA-DNA helicase assay, DRIP-seq (genome-wide R-loop mapping), DNA damage markers, replication fork assays, overexpression rescue experiments Genes & Development High 32439635
2020 DDX39B facilitates DNA repair by homologous recombination through binding to and stabilizing BRCA1 mRNA; DDX39B-deficient cells show impaired ssDNA formation and RAD51 accumulation at DSB sites, and hypersensitivity to platinum and PARPi. RNA immunoprecipitation, mRNA stability assay, DNA damage repair assays (ssDNA formation, RAD51 foci), CRISPR/siRNA depletion, mouse knockout phenotype Oncogene Medium 32989256
2020 DDX39B inhibits NF-κB activity by inhibiting p65 phosphorylation through interaction with the pattern recognition receptor LGP2, a pathway requiring cellular response to cytoplasmic dsRNA. DDX39B protein abundance is regulated by PIASx-β-mediated sumoylation that promotes poly-ubiquitination and degradation. Streptavidin-agarose pull-down with κB DNA probes, RNAi, CRISPR/Cas9 KO, p65 phosphorylation assay, Co-IP with LGP2, sumoylation/ubiquitination assays BMC Biology Medium 32209106
2020 UAP56 features two NP-binding sites: the RecA-domain core and an N-terminal extension (NTE) that recognizes the nucleic acid-binding region of influenza NP. UAP56-NTE binding to NP is mutually exclusive with RNA binding to NP, explaining how UAP56 chaperones RNA-free NP for vRNP assembly. In vitro binding assay with recombinant proteins, domain mapping, competition assay between UAP56-NTE and RNA for NP binding Biochemical and Biophysical Research Communications Medium 32085897
2021 DDX39B binds directly to FUT3 pre-mRNA, promotes its splicing, and enhances FUT3 mRNA export; elevated FUT3 leads to fucosylation of TGFβR-I, activating TGFβ signaling and driving EMT in colorectal cancer. RIP-seq, RNA-seq, minigene splicing assay, nuclear/cytoplasmic RNA fractionation, gain/loss-of-function assays Cell Death & Disease Medium 33436563
2022 DDX39B directly binds to the first exon of CDK6 and CCND1 pre-mRNAs (confirmed by RIP-seq) and promotes their splicing; CDK6/CCND1 upregulation drives G1/S cell cycle transition and CRC cell proliferation. RIP-seq, in vitro splicing RT-PCR, flow cytometry, rescue experiments, orthotopic xenograft model Cell Death Discovery Medium 35046400
2023 DDX39B controls splicing of FOXP3 pre-mRNA introns that have C-rich/U-poor polypyrimidine tracts; DDX39B knockdown reduces FOXP3 expression, resulting in loss of immune-regulatory and gain of immune-effector gene expression signatures in T cells. DDX39B also controls splicing of many other MS susceptibility genes. siRNA knockdown, RT-PCR splicing assays, transcriptomic profiling of human T cells eLife High 37261960
2023 Crystal structure of a yeast Tho1 (SARNP)/DDX39B/RNA complex reveals that SARNP engages DDX39B through tandem DDX39B-interacting motifs, forming a high-order complex where human SARNP can bind up to five DDX39B molecules simultaneously. SARNP knockdown preferentially affects export of GC-rich RNAs. X-ray crystallography, biochemical reconstitution, RNA-seq from SARNP knockdown cells Cell Reports High 37578863
2023 DDX39B directly interacts with SREBP1 protein, stabilizes SREBP1 by preventing FBXW7-mediated ubiquitination and degradation, and promotes SREBP1 nuclear translocation and transcriptional activation of lipogenic genes in hepatocellular carcinoma. Co-immunoprecipitation, immunofluorescence for nuclear translocation, luciferase transcriptional activity assay, ubiquitination assay, xenograft mouse model Cellular Oncology Medium 37052853
2024 DDX39B specifically regulates splicing of pre-mRNAs with C-rich/U-poor polypyrimidine tracts (e.g., IL7R exon 6, FOXP3 introns) that DDX39A cannot complement; the variant polypyrimidine tract is necessary and sufficient for DDX39B-specific dependency. siRNA knockdown of DDX39A and DDX39B individually and combined, minigene splicing assay with polypyrimidine tract mutations, RT-PCR Nucleic Acids Research High 38801080
2024 FOXP3 introns with C-rich/U-poor polypyrimidine tracts cause deficient DDX39B recruitment and inefficient pre-spliceosome assembly; the altered U2AF2 conformation on C-rich tracts has lower affinity for DDX39B, explaining how DDX39B levels gate commitment complex to pre-spliceosome conversion on these introns. In vitro splicing commitment complex assembly assay, U2AF2 binding assays, spliceosome assembly analysis RNA High 38575347
2024 Cryo-EM and crystal structures of TREX-2/DDX39B and TREX-2.1/DDX39B complexes reveal that a conserved trigger loop in GANP (TREX-2) and LENG8 (TREX-2.1) regulates DDX39B release from mRNPs; LENG8 knockdown selectively affects nucleocytoplasmic ratio of GC-rich mRNAs. Cryo-EM structure determination, X-ray crystallography, mutagenesis of trigger loop, RNA-seq from LENG8 knockdown cells Nature Communications High 40595470
2024 Unique structural features of UAP56 (versus URH49) are responsible for formation of their respective distinct apo-complexes (apo-TREX vs. apo-AREX); chimeric mutant analysis identifies terminal regions critical for complex formation specificity. Structural comparison, chimeric mutant analysis, co-immunoprecipitation, mRNA export assays Nature Communications Medium 38225262
2024 DDX39B promotes splicing and cytoplasmic export of GPX4 pre-mRNA; inhibition of DDX39B ATPase activity by CCT018159 represses GPX4 pre-mRNA splicing and export, sensitizing HCC cells to sorafenib-induced ferroptosis. RIP, mRNA splicing assays, nuclear/cytoplasmic fractionation, ATPase inhibitor (CCT018159) treatment, lipid peroxidation and ferroptosis assays Biochemical Pharmacology Medium 38701867
2025 DDX39B undergoes K63-linked ubiquitination mediated by TRIM28 E3 ligase at residues Lys241, Lys384, and Lys398 (via interaction through DDX39B Pro322), leading to DDX39B protein stabilization; stabilized DDX39B then directly binds E-cadherin (ECAD) and promotes its lysosomal degradation by recruiting Src and Hakai, activating β-catenin signaling—independently of RNA helicase activity. Co-immunoprecipitation, ubiquitination assay, immunofluorescence, lysosome inhibitor experiments, structure-based virtual screening 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 editing efficiency genome-wide. Genome-scale CRISPR screen, single-cell CRISPR RNA-seq (scCREDIT-seq), transcriptome-wide A-to-I editing profiling Cell Reports Medium 40652511
2025 The PAXT-associated LENG8-PCID2-SEM1 (LENG8-PS) trimeric complex is structurally and functionally equivalent to the GANP-PCID2-SEM1 trimer of TREX-2, and competes with NPC-associated TREX-2 for UAP56-bound pA+ RNPs; PAXT releases RNAs from UAP56 for nuclear exosome decay while TREX-2 releases them for export, thereby governing nuclear RNA fate. Structural analysis, mutagenesis, transcriptomic analysis (RNA fate mapping), biochemical reconstitution bioRxivpreprint Medium
2017 UAP56 stimulates trimeric NP formation from monomeric NP and forms a complex with trimeric NP (two trimeric NPs bridged by UAP56); trimeric NP has higher RNA-binding activity, and UAP56 facilitates viral RNP assembly by promoting NP trimerization and controlled NP transfer to viral RNA. Gel filtration chromatography, atomic force microscopy, NP oligomerization assay, RNA-binding assay Scientific Reports Medium 29070793
2018 DDX39B affects levels of pre-ribosomal RNA by regulating its stability and synthesis, thereby promoting global translation and cell proliferation independently of its mRNA export function. Pre-rRNA stability and synthesis assays, polysome profiling, overexpression and knockdown experiments RNA Biology Medium 30176153
2002 HEL (Chironomus UAP56) binds to Balbiani ring pre-mRNP cotranscriptionally and in an intron-independent manner, accompanies the mRNP to the nuclear pore, and is released during translocation to the cytoplasm before Aly/REF release. Immunoelectron microscopy on polytene chromosomes and nuclear pore complexes Current Biology High 12015125
2025 De novo and inherited missense variants in DDX39B impair TREX complex assembly (variants p.Gly92Asp and c.433-1G>T) or cause aberrant splicing (variants p.Gly37Cys, p.Arg123Gln, c.433-1G>T), establishing DDX39B loss-of-function as a cause of a neurodevelopmental syndrome. Zebrafish morpholino knockdown of DDX39B causes reduced head size and body length rescued by DDX39B mRNA. In vitro Co-IP with HA-tagged variants, blood transcriptomics (aberrant splicing), Drosophila transgenic overexpression lethality assay, zebrafish morpholino knockdown with mRNA rescue Brain High 39918047

Source papers

Stage 0 corpus · 99 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 330 11675789
2001 The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Current biology : CB 198 11696332
2012 UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 184 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 111 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 97 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
2009 BAT1, a bidirectional amino acid transporter in Arabidopsis. Planta 63 19199104
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
2001 The central MHC gene, BAT1, may encode a protein that down-regulates cytokine production. Genes to cells : devoted to molecular & cellular mechanisms 58 11380625
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
1995 The BAT1 gene in the MHC encodes an evolutionarily conserved putative nuclear RNA helicase of the DEAD family. Genomics 51 7601445
2016 The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation. Biochemical and biophysical research communications 50 28025139
2013 Arabidopsis DEAD-box RNA helicase UAP56 interacts with both RNA and DNA as well as with mRNA export factors. PloS one 48 23555998
2011 Saccharomyces cerevisiae Bat1 and Bat2 aminotransferases have functionally diverged from the ancestral-like Kluyveromyces lactis orthologous enzyme. PloS one 46 21267457
2006 BAT1, a putative anti-inflammatory gene, is associated with chronic Chagas cardiomyopathy. The Journal of infectious diseases 44 16619187
2020 Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA. Oncogene 37 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
2017 Reduced Production of Higher Alcohols by Saccharomyces cerevisiae in Red Wine Fermentation by Simultaneously Overexpressing BAT1 and Deleting BAT2. Journal of agricultural and food chemistry 31 28721728
2012 BAT1, a putative acyltransferase, modulates brassinosteroid levels in Arabidopsis. The Plant journal : for cell and molecular biology 29 23020607
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
2005 The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy. Tissue antigens 26 16101831
2005 Alpha-actinin 4 and BAT1 interaction with the cytochrome c promoter upon skeletal muscle differentiation. Current genetics 26 16331456
2023 DDX39B facilitates the malignant progression of hepatocellular carcinoma via activation of SREBP1-mediated de novo lipid synthesis. Cellular oncology (Dordrecht, Netherlands) 25 37052853
2022 The RNA helicase UAP56 and the E3 ubiquitin ligase COP1 coordinately regulate alternative splicing to repress photomorphogenesis in Arabidopsis. The Plant cell 25 35920787
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
2003 Alleles of the proximal promoter of BAT1, a putative anti-inflammatory gene adjacent to the TNF cluster, reduce transcription on a disease-associated MHC haplotype. Genes to cells : devoted to molecular & cellular mechanisms 24 12653967
2008 Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease. Journal of neuroinflammation 23 18715507
2007 Association of variants in the BAT1-NFKBIL1-LTA genomic region with protection against myocardial infarction in Europeans. Human molecular genetics 23 17517687
2011 The cellular DExD/H-box RNA-helicases UAP56 and URH49 exhibit a CRM1-independent nucleocytoplasmic shuttling activity. PloS one 22 21799930
2011 Association of variants in BAT1-LTA-TNF-BTNL2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of Indian population. Human genetics 22 22071774
2004 Polymorphisms at positions -22 and -348 in the promoter of the BAT1 gene affect transcription and the binding of nuclear factors. Human molecular genetics 20 15028669
1999 Characterisation of the human central MHC gene, BAT1: genomic structure and expression. Experimental and clinical immunogenetics 20 10343160
2016 UAP56 is a conserved crucial component of a divergent mRNA export pathway in Toxoplasma gondii. Molecular microbiology 19 27542978
1992 Ancestral haplotypes carry haplotypic and haplospecific polymorphisms of BAT1: possible relevance to autoimmune disease. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 19 1352699
2018 Valine biosynthesis in Saccharomyces cerevisiae is regulated by the mitochondrial branched-chain amino acid aminotransferase Bat1. Microbial cell (Graz, Austria) 18 29850466
2023 Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly. Cell reports 16 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 14 36109793
2021 Preparation of chitosan from waste shrimp shells fermented with Paenibacillus jamilae BAT1. International journal of biological macromolecules 14 33989684
2020 Cellular mRNA export factor UAP56 recognizes nucleic acid binding site of influenza virus NP protein. Biochemical and biophysical research communications 14 32085897
2008 BAT1 promoter polymorphism is associated with rheumatoid arthritis susceptibility. The Journal of rheumatology 14 18381799
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
2014 Genetic variation on the BAT1-NFKBIL1-LTA region of major histocompatibility complex class III associates with periodontitis. Infection and immunity 11 24566624
2025 Structural mechanism of DDX39B regulation by human TREX-2 and a related complex in mRNP remodeling. Nature communications 10 40595470
2017 Cellular splicing factor UAP56 stimulates trimeric NP formation for assembly of functional influenza viral ribonucleoprotein complexes. Scientific reports 10 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
2015 Stress-induced Oryza sativa BAT1 dual helicase exhibits unique bipolar translocation. Protoplasma 9 25772680
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
2005 Co-localization and interaction of b0,+-type amino acid transporter 1 (BAT1) with caveolin-1 in rat kidney. Journal of nephrology 7 16358225
2002 Does the rat have an H2-D orthologue next to Bat1? Immunogenetics 7 11904681
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
2025 De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome. Brain : a journal of neurology 5 39918047
2025 DDX39B K63-linked ubiquitination mediated by TRIM28 promotes NSCLC metastasis by enhancing ECAD lysosomal degradation. Signal transduction and targeted therapy 5 40664668
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
2015 Both BAT1 and ARO8 are responsible for unpleasant odor generation in halo-tolerant yeast Zygosaccharomyces rouxii. Applied microbiology and biotechnology 5 25982000
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
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 4 37918588
2024 Inefficient recruitment of DDX39B impedes pre-spliceosome assembly on FOXP3 introns. RNA (New York, N.Y.) 3 38575347
2019 UAP56 associates with DRM2 and is localized to chromatin in Arabidopsis. FEBS open bio 3 30951268
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
2025 Multimodal CRISPR screens uncover DDX39B as a global repressor of A-to-I RNA editing. Cell reports 2 40652511
2022 CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene-Gene Interactions Are Associated with Restenosis after Coronary Stenting. Biomolecules 2 35740890
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
2022 HLA-BAT1 alters migration, invasion and pro-inflammatory cytokines in prostate cancer. Frontiers in oncology 0 36505884