Affinage

DDX1

ATP-dependent RNA helicase DDX1 · UniProt Q92499

Length
740 aa
Mass
82.4 kDa
Annotated
2026-06-09
76 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX1 is a DEAD-box ATP-dependent RNA helicase that functions across multiple RNA-metabolic processes, with an ATPase activity that hydrolyzes only ATP/dATP and is stimulated by single-stranded RNA ≥10 nt, blunt dsRNA, and RNA/DNA hybrids, exhibiting cooperative RNA/ATP binding and exceptionally tight ADP binding that arrests it in a dead-end state (PMID:39895751, PMID:25690890). It is a structural and catalytic subunit of the human RTCB tRNA ligase complex, tethered to RTCB via its C-terminal helix within a CGI-99/DDX1/FAM98B α-helical bundle, where its helicase activity is specifically required for tRNA splicing but not for XBP1 mRNA splicing [PMID:bio_10.1101_2025.08.01.668197, PMID:39833356, PMID:24870230]. In the nucleus DDX1 resolves co-transcriptional secondary structures: it unwinds G-quadruplex switch transcripts to generate R-loops that target AID and drive immunoglobulin class switch recombination (PMID:29731414), is recruited via RIF1 to DNA double-strand breaks to load BLM and promote homologous recombination (PMID:28544931), and participates in R-loop processing at transcription termination and during RNA Pol II elongation in concert with CstF-64, Gle1, and a TFIIH-CAK–SFPQ–NONO assembly (PMID:11598190, PMID:32755435, PMID:40757642). DDX1 also acts in pri-miRNA processing as an ATM-phosphorylated component of the Drosha/DGCR8 microprocessor (PMID:25176654), in pre-mRNA 3'-end cleavage through CstF-64 (PMID:11598190), and in alternative splicing through interaction with hnRNP K (PMID:12183465, PMID:41197750). In the cytoplasm it senses dsRNA as part of a DDX1–DDX21–DHX36–TRIF complex to activate type I interferon responses (PMID:21703541) and is recruited to stress granules to maintain stress-response mRNAs during oxidative stress (PMID:35752363). Multiple viruses co-opt DDX1: it is recruited to GSK-3-phosphorylated coronavirus nucleocapsid complexes to enable template readthrough during RNA synthesis (PMID:25299332, PMID:41903808) and serves as a Rev cofactor promoting HIV-1 Rev oligomerization on the RRE (PMID:21763499, PMID:22051512). Mouse and Drosophila knockouts establish essential developmental roles, with murine Ddx1 loss causing pre-implantation embryonic lethality (PMID:25909345, PMID:31330130, PMID:26433063). DDX1 activity and localization are tuned by phosphorylation (ATM, GSK-3), arginine methylation (PRMT1) coupled to USP10/USP45 deubiquitination, lysine methylation (EZH2), and crotonylation (GCN5/HDAC1) (PMID:25176654, PMID:41668296, PMID:41468936, PMID:40610464, PMID:41197750).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 Medium

    Established that DDX1 protein partitions between nucleus and cytoplasm and that its subcellular distribution shifts with overexpression, framing localization as a regulated, dosage-sensitive property.

    Evidence Immunofluorescence and blotting across DDX1-amplified versus non-amplified neuroblastoma/retinoblastoma cell lines

    PMID:9694872

    Open questions at the time
    • Functional consequence of cytoplasmic redistribution not directly tested
    • No mechanism for the localization switch identified
  2. 2001 High

    First placed DDX1 in a defined nuclear RNA-processing context by demonstrating close physical proximity to the 3'-end cleavage factor CstF-64 in cleavage bodies.

    Evidence Immunofluorescence, FRET (<10 nm), and co-immunoprecipitation

    PMID:11598190

    Open questions at the time
    • Direct catalytic role in 3'-end processing not demonstrated
    • Whether DDX1 helicase activity acts on cleavage substrates unknown
  3. 2002 High

    Defined DDX1 as a poly(A)-binding RNA helicase whose ATPase is RNA- but not DNA-stimulated and which physically partners hnRNP K, linking it to mRNA biogenesis.

    Evidence GST pulldown, LC-MS/MS, in vitro ATPase and dsRNA unwinding assays, domain mapping

    PMID:12183465

    Open questions at the time
    • Unwinding required the immunoprecipitated complex, not purified DDX1 alone
    • Physiological RNA substrates not defined
  4. 2010 High

    Revealed that coronaviruses recruit DDX1 via nsp14, with DDX1 relocalizing to the cytoplasm during infection to support viral replication.

    Evidence Yeast two-hybrid, reciprocal Co-IP in infected cells, domain mapping, siRNA/mutant overexpression with replication readout (IBV, SARS-CoV)

    PMID:20573827

    Open questions at the time
    • Helicase activity requirement for this step not resolved
    • Mechanism of DDX1 relocalization during infection unknown
  5. 2011 High

    Identified a cytosolic dsRNA-sensing role: DDX1 within a DDX1–DDX21–DHX36–TRIF complex triggers type I IFN, establishing innate immune sensing as a distinct DDX1 function.

    Evidence Poly I:C-binding protein isolation, domain mapping, shRNA knockdown with IFN/cytokine readout across multiple viruses

    PMID:21703541

    Open questions at the time
    • Structural basis of complex assembly not resolved
    • Whether helicase activity is required for sensing not tested
  6. 2011 High

    Mechanistically dissected DDX1 as an HIV-1 Rev cofactor, showing it accelerates productive Rev oligomerization on the RRE rather than acting on the RNA itself.

    Evidence Recombinant biochemistry, ATPase assays, single-molecule TIRF Rev-RRE assembly kinetics, siRNA knockdown with HIV production readout

    PMID:21763499 PMID:22051512

    Open questions at the time
    • In vivo relevance of ATPase to Rev function not fully resolved
    • Endogenous RNA targets of this activity beyond Rev unknown
  7. 2014 High

    Defined DDX1's enzymatic role within the RTCB tRNA ligase complex, showing it facilitates formation of the RTCB-guanylate intermediate central to mammalian RNA ligation.

    Evidence Orthologous group analysis and biochemical complementation of RTCB-guanylate intermediate formation

    PMID:24870230

    Open questions at the time
    • Step at which helicase activity contributes not defined here
    • Substrate specificity within the complex not addressed
  8. 2014 High

    Connected DDX1 to the DNA-damage response by showing ATM-phosphorylated DDX1 promotes pri-miRNA maturation within the microprocessor, with tumor-suppressive consequences.

    Evidence RNA-IP, miRNA profiling, ATM kinase assays, knockdown/overexpression, syngeneic mouse tumor model

    PMID:25176654

    Open questions at the time
    • How phosphorylation alters microprocessor activity mechanistically unclear
    • Determinants of pri-miRNA subset selectivity unknown
  9. 2015 High

    Provided the first quantitative enzymology and atomic structural information for DDX1, defining cooperative RNA/ATP binding, dead-end ADP capture, and the SPRY domain interaction surface.

    Evidence Equilibrium and transient kinetics, nucleotide-binding assays, 2.0 Å crystal structure of the SPRY domain

    PMID:25690890 PMID:26323305

    Open questions at the time
    • Nucleotide exchange factor for ADP recycling not identified
    • Full-length helicase structure absent
  10. 2015 Medium

    Established DDX1 as developmentally essential, with mouse knockout causing pre-implantation lethality and Drosophila loss causing fertility and stress-splicing defects.

    Evidence Constitutive mouse KO with embryo staging; Drosophila null with RNA-seq, Sirup mRNA binding, and genetic epistasis

    PMID:25909345 PMID:26433063

    Open questions at the time
    • Molecular cause of 2-4 cell arrest not resolved
    • Transgenerational non-genetic lethality mechanism unexplained
  11. 2017 Medium

    Placed DDX1 in homologous recombination repair, showing RIF1-dependent recruitment to DSBs and a requirement for BLM helicase loading, with distinct nucleic-acid dependencies.

    Evidence Co-IP, laser-induced DSBs, knockdown, HR assay, BLM chromatin-loading assay, RNA-DNA hybrid dependency analysis

    PMID:28544931

    Open questions at the time
    • Direct catalytic contribution of DDX1 helicase at DSBs not established
    • Single lab without reciprocal structural validation
  12. 2018 High

    Demonstrated that DDX1 unwinds G-quadruplex switch transcripts to generate R-loops that target AID, mechanistically linking DDX1 catalysis to immunoglobulin class switch recombination.

    Evidence In vivo CSR assays, chemical G4 stabilization, ATPase-dead dominant-negative mutant, R-loop immunoprecipitation

    PMID:29731414

    Open questions at the time
    • Recruitment mechanism to switch regions not defined
    • Genome-wide breadth of G4-to-R-loop activity not mapped here
  13. 2018 Medium

    Identified tissue-specific RNA roles in pancreatic β cells, with DDX1 regulating insulin mRNA translation and calcium-channel alternative splicing, both tied to a phospho-switch at S295.

    Evidence RNA antisense purification-MS, CLIP-seq, RNA-seq, phospho-site mapping, eIF3A/eIF4B Co-IP, calcium influx and insulin secretion assays

    PMID:29679569 PMID:30295850

    Open questions at the time
    • Kinase responsible for S295 phosphorylation not identified
    • Single-lab findings without independent replication
  14. 2019 Medium

    Showed DDX1 localizes to RNA-dependent cytoplasmic granules in oocytes/embryos and binds specific maternal mRNAs required for early development, connecting localization to its embryonic-essential phenotype.

    Evidence Immunofluorescence, RNase-dependency of localization, RNA-IP from 2-cell embryos, Ddx1 KO mouse

    PMID:31330130

    Open questions at the time
    • How DDX1 maintains maternal mRNAs mechanistically unclear
    • Granule composition not fully defined
  15. 2022 Medium

    Extended DDX1's cytoplasmic RNA-protective role to stress granules and described a novel RNA-containing membrane organelle (MARV) coupling DDX1 to calcium and mitochondrial homeostasis.

    Evidence Stress granule assays with multiple stressors, RIP-seq, RNA-binding mutant analysis; EM, calcium imaging, mitochondrial/ROS assays in KO embryos

    PMID:35752363 PMID:35778392

    Open questions at the time
    • MARV biogenesis and DDX1's enzymatic role within it unresolved
    • Mechanism linking DDX1 RNA binding to mRNA stabilization undefined
  16. 2025 High

    Defined substrate specificity within the RTCB complex—helicase activity is required for tRNA but not XBP1 splicing—and resolved complex architecture by cryo-EM, tethering DDX1 to RTCB via its C-terminal helix.

    Evidence Conditional KO with helicase-dead rescue and dual substrate (tRNA vs XBP1) assays; cryo-EM with structure-based mutagenesis (preprint)

    PMID:39833356 PMID:bio_10.1101_2025.08.01.668197

    Open questions at the time
    • Why helicase activity is dispensable for XBP1 splicing not mechanistically explained
    • Cryo-EM structure is a preprint
  17. 2025 Medium

    Mapped a dense post-translational regulatory layer—PRMT1 arginine methylation with USP10/USP45 deubiquitination, EZH2 lysine methylation, and GCN5/HDAC1 crotonylation—that controls DDX1 localization, stability, and splicing-factor interactions in disease contexts.

    Evidence Modification proteomics/MS site mapping, writer/eraser identification, Co-IP, splicing RNA-seq/ATAC-seq, and in vivo tumor and disc-degeneration models

    PMID:40610464 PMID:41197750 PMID:41468936 PMID:41668296

    Open questions at the time
    • Crosstalk and hierarchy among the PTMs not integrated
    • Each modification characterized in a single disease context only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DDX1's single helicase activity is partitioned and selectively deployed across its many complexes (RTCB ligation, R-loop processing, innate sensing, granule maintenance, viral RNA synthesis) remains unresolved.
  • No unified model linking substrate/cofactor context to which DDX1 function is engaged
  • No full-length structure with bound substrate
  • Nucleotide exchange factor for ADP recycling unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140657 ATP-dependent activity 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4 GO:0005654 nucleoplasm 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 3
Partners
CSTF2EXOSC3FAM98BGLE1HNRNPKRIF1RTCBUSP45
Complex memberships
DDX1-DDX21-DHX36-TRIF dsRNA-sensing complexDrosha/DGCR8 microprocessorRTCB tRNA ligase complexTFIIH-CAK–DDX1–SFPQ–NONO R-loop processing assembly

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 DDX1, DDX21, and DHX36 form a cytosolic complex with the adaptor TRIF to sense dsRNA in myeloid dendritic cells; DDX1 binds poly I:C via its Helicase A domain, while DHX36 and DDX21 bind the TIR domain of TRIF via their HA2-DUF and PRK domains, respectively. Knockdown of DDX1 blocked type I IFN and cytokine responses to poly I:C, influenza A virus, and reovirus. Isolation/sequencing of poly I:C-binding proteins, shRNA knockdown, domain mapping, cytosolic localization confirmed independently of endosomes Immunity High 21703541
2014 Phosphorylation of the coronavirus nucleocapsid (N) protein by GSK-3 recruits RNA helicase DDX1 to the N-containing complex, facilitating template readthrough during transcription and enabling synthesis of longer subgenomic mRNAs and full-length genomic RNA. DDX1 knockdown or loss of helicase activity markedly reduces longer sgmRNA levels. GSK-3 inhibition, DDX1 knockdown, helicase-dead mutant expression, quantitative RT-PCR for sgmRNA species Cell host & microbe High 25299332
2018 DDX1 binds G-quadruplex (G4) structures in intronic switch transcripts at the IgH locus and converts them into R-loops, thereby targeting AID to S-regions to promote class switch recombination (CSR). An ATPase-deficient DDX1 mutant acts as dominant-negative, reducing R-loop levels over S-regions and CSR efficiency. In vivo CSR assays, chemical G4 stabilization, ATPase-deficient dominant-negative mutant, R-loop immunoprecipitation Molecular cell High 29731414
2014 DDX1 is a component of the human tRNA splicing ligase complex (tRNA-LC); together with archease, DDX1 facilitates formation of the RTCB-guanylate intermediate central to mammalian RNA ligation, defining DDX1's enzymatic role within this complex. Eukaryotic orthologous group analysis, biochemical complementation assay for RTCB-guanylate intermediate formation Nature High 24870230
2010 DDX1 interacts with coronavirus (IBV and SARS-CoV) nonstructural protein 14 (nsp14); the interaction maps to the C-terminal region of DDX1 (motifs V and VI) and the N-terminal portion of nsp14. DDX1 is relocalized from nucleus to cytoplasm upon IBV infection, and either siRNA knockdown or overexpression of a DDX1 mutant reduced IBV replication. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, subcellular fractionation/immunofluorescence, viral replication assay Journal of virology High 20573827
2014 DDX1 promotes maturation of a subset of primary miRNAs (including miR-200 family members) by functioning as a regulatory component of the Drosha/DGCR8 microprocessor. ATM-mediated phosphorylation of DDX1 facilitates this induction after DNA damage. DDX1 inhibition promotes ovarian tumor growth and metastasis in a syngeneic mouse model. RNA-IP, miRNA profiling, ATM kinase assays, DDX1 knockdown/overexpression, syngeneic mouse tumor model Cell reports High 25176654
2001 DDX1 colocalizes with cleavage stimulation factor CstF-64 in nuclear cleavage bodies and resides within 10 nm of CstF-64 (demonstrated by FRET). Co-immunoprecipitation shows DDX1 is in the same complex as CstF-64, implicating DDX1 in 3'-end cleavage and polyadenylation of pre-mRNAs. Immunofluorescence, fluorescence resonance energy transfer (FRET), co-immunoprecipitation Molecular biology of the cell High 11598190
2002 DDX1 physically interacts with hnRNP K via the N-terminal 1–276 amino acids of hnRNP K; this interaction is disrupted by poly(A), poly(C), and poly(U) RNA substrates. DDX1 is a homopolymeric poly(A) RNA-binding protein whose ATPase activity is stimulated by homopolymeric RNAs and total yeast RNA but not by DNA. The immunoprecipitated DDX1 complex (but not purified DDX1 alone) unwinds dsRNA with single-stranded poly(A) overhangs. GST affinity chromatography, LC-MS/MS, in vitro binding assay, co-immunoprecipitation, ATPase assay, RNA unwinding assay The Journal of biological chemistry High 12183465
2011 DDX1 is an RNA-activated ATPase that binds HIV-1 Rev in an RNA-independent manner and forms complexes with Rev-bound RNA. DDX1 is required for both Rev activity and HIV-1 production from infected cells (demonstrated by RNA silencing). Rev-bound RNA is equally effective as protein-free RNA at stimulating DDX1 ATPase activity. Recombinant protein biochemistry, gel-filtration, CD spectroscopy, fluorescent Rev binding assay, cell-based Co-IP, ATPase assay, gel mobility shift, siRNA knockdown, HIV production assay Journal of molecular biology High 22051512
2011 DDX1 promotes oligomerization of HIV-1 Rev on the Rev response element (RRE) by eliminating nonproductive nucleation events and accelerating early Rev monomer binding steps, without altering dissociation rates. This effect is enhanced by non-hydrolyzable ATP (AMP-PNP) but not ADP. DDX1 targets Rev rather than the RRE and can rescue oligomerization of a Rev mutant that cannot assemble beyond a monomer. Single-molecule total internal reflection fluorescence microscopy (TIRF), fluorescently labeled Rev, real-time Rev-RRE assembly/dissociation kinetics Journal of molecular biology High 21763499
2009 DDX1 interacts with NF-κB subunit RelA (p65) and acts as a co-activator to enhance NF-κB-mediated transcription. The interaction maps to the C-terminal transactivation domain of RelA and the N-terminal ATPase/helicase domain of DDX1. A DDX1 dominant-negative mutant lacking ATPase/helicase activity loses transcriptional co-activator function. Mammalian two-hybrid, co-immunoprecipitation, confocal microscopy, chromatin immunoprecipitation, NF-κB reporter gene assay, siRNA knockdown, domain mapping Journal of cellular biochemistry Medium 19058135
2005 DDX1 functions as a cellular co-factor for HIV-1 Rev in the nucleus/nucleolus; low endogenous DDX1 in human astrocytes shifts Rev localization from nuclear/nucleolar to cytoplasmic dominance. Exogenous DDX1 expression in astrocytes restores nuclear Rev localization and increases HIV-1 viral production. HIV-1 pseudotyped infection, semi-quantitative RT-PCR for spliced/unspliced RNA, DDX1 overexpression, Rev immunofluorescence localization Virology Medium 15892970
2015 DDX1 bodies, cleavage bodies, Cajal bodies, and gems are distinct nuclear suborganelles whose associations are cell-cycle-regulated; CstF-64-containing cleavage bodies are primarily found during S phase and are sensitive to DNA replication inhibitors; all four bodies associate during S phase with cleavage bodies colocalizing with DDX1 bodies. Latrunculin B (actin polymerization inhibitor) causes formation of nuclear spicules containing CstF-64, CPSF-100, RNA, and RNA Pol II. Immunofluorescence throughout cell cycle, inhibitors of transcription/DNA replication/actin polymerization, live-cell imaging Molecular biology of the cell Medium 16371507
1998 DDX1 protein is found in both nucleus and cytoplasm of DDX1-amplified neuroblastoma and retinoblastoma cell lines, but is localized primarily to the nucleus of non-amplified cells, establishing overexpression-dependent cytoplasmic redistribution. Immunofluorescence with polyclonal anti-DDX1 antibodies, Western blot, Northern blot The Journal of biological chemistry Medium 9694872
2015 Biochemical characterization of DDX1 shows exceptionally tight ADP binding (three orders of magnitude tighter than ATP), arresting the enzyme in a potential ADP dead-end conformation, suggesting DDX1 requires a nucleotide exchange factor for recycling. Strong cooperativity in RNA and ATP binding to DDX1 was observed, where either ligand alone partially shifts the enzyme from 'open' to 'closed' state. Equilibrium titrations, transient kinetics, nucleotide binding assays Nucleic acids research High 25690890
2015 Crystal structure of the SPRY domain of human DDX1 (hDSPRY) resolved at 2.0 Å reveals two layers of concave antiparallel β-sheets and a conserved patch of positive surface charge proposed as a protein–protein interaction surface, providing the first structural information on any DDX1 domain. X-ray crystallography at 2.0 Å resolution Acta crystallographica. Section F, Structural biology communications High 26323305
2015 Drosophila Ddx1 null flies are viable but reduced in size, with females showing reduced fertility due to egg chamber autophagy and males being sterile due to disrupted spermatogenesis. Ddx1 directly binds Sirup mRNA and regulates its differential splicing; double mutant (Ddx1 null + Sirup RNAi) causes epistatic lethality not seen in single mutants, suggesting Ddx1 acts in a stress-induced splicing pathway involving Sirup. Drosophila null mutation, comparative RNA-seq, RNA binding assay (Sirup mRNA), genetic epistasis with dsRNA knockdown Developmental biology Medium 26433063
2015 Homozygous Ddx1 knockout in mice causes embryonic lethality prior to E3.5, with embryos stalling at the 2-4 cell stage. Heterozygote crosses reveal a transgenerational wild-type lethality phenotype transmitted through Ddx1*(/-) parents independently of sex, via a non-genetic mechanism. Constitutive Ddx1 knockout mouse generation, embryo staging, genotyping of progeny from heterozygote crosses Scientific reports Medium 25909345
2019 DDX1 protein localizes exclusively to cytoplasmic granules in oocytes and early mouse embryos, requiring RNA for retention at these sites. Homozygous Ddx1 KO causes stalling at 2-4 cell stages. DDX1 RNA-immunoprecipitation from 2-cell embryos identified five maternal mRNAs (Ago2, Zar1, Tle6, Floped, Tif1α) as preferential DDX1-binding targets required for embryonic development past the 1-2 cell stage. Immunofluorescence in oocytes/embryos, RNA-IP from 2-cell embryos, Ddx1 knockout mouse model, RNA dependency of localization tested by RNase treatment Developmental biology Medium 31330130
2022 DDX1 is recruited to stress granules (SGs) in cells exposed to arsenite, hydrogen peroxide, and thapsigargin. DDX1 depletion delays resolution of arsenite-induced SGs. RNA-IP-seq identifies stress response mRNAs bound by DDX1, and the amount of these target RNAs bound to DDX1 and their overall levels increase during stress in a DDX1-dependent manner. RNA-binding is required for mRNA maintenance but not for DDX1 localization to SGs. Immunofluorescence, stress granule assays, RNA immunoprecipitation-seq (RIP-seq), DDX1 KD, RNA-binding mutant analysis The Journal of biological chemistry Medium 35752363
2022 DDX1 forms membrane-bound calcium-containing organelles (Membrane Associated RNA-containing Vesicles, MARVs) with a nucleic acid core in early mouse embryos. Ddx1 KO disrupts calcium distribution, increases mitochondrial membrane potential, mitochondrial activity, and reactive oxygen species in embryos, indicating DDX1/MARVs regulate calcium-controlled mitochondrial function. Electron microscopy, calcium imaging, Ddx1 KO embryos, mitochondrial potential/ROS assays, RNA sequencing of embryos Nature communications Medium 35778392
2021 Loss of Ddx1 in mouse embryonic stem cells causes rRNA processing defects, thereby activating the ribosome stress-p53 pathway. This was identified using a conditional knockout system with inducible gene deletion. Conditional Ddx1 knockout ESCs, rRNA processing assay, p53 pathway activation readout Nucleic acids research Medium 33503245
2025 DDX1 enzymatic (helicase) activity is specifically required for tRNA splicing in vivo but not for ER stress-induced XBP1 mRNA splicing. A helicase-inactive DDX1 mutant fails to rescue tRNA splicing defects in DDX1-deficient cells, establishing DDX1's catalytic role within the RTCB tRNA ligase complex specifically for tRNA substrates. DDX1 conditional KO in human U2OS cells (CRISPR), tRNA splicing assays, XBP1 splicing assays under ER stress, rescue with wild-type vs. helicase-dead DDX1 Communications biology High 39833356
2017 DDX1 interacts with RIF1, and DDX1 recruitment to DNA double-strand breaks (DSBs) is dependent on RIF1; RIF1 depletion abolishes DDX1-mediated facilitation of homologous recombination at DSBs. Both DDX1 and RIF1 are required for chromatin loading of BLM helicase at DSBs. RNA-DNA hybrids are required for DDX1 accumulation at DSBs, whereas single-strand RNA is required for RIF1 accumulation. Co-IP, co-localization throughout cell cycle, laser-induced DSBs, RIF1/DDX1 knockdown, HR assay, BLM chromatin loading assay, nucleic acid dependency analysis DNA repair Medium 28544931
2018 DDX1 binds insulin mRNA in pancreatic β cells; palmitate-induced phosphorylation of DDX1 at S295 dissociates DDX1 from insulin mRNA, suppressing insulin translation. DDX1 interacts with translation initiation factors eIF3A and eIF4B to promote translation. DDX1 knockdown eliminates palmitate-induced repression of insulin translation. RNA antisense purification coupled with MS, DDX1 KD/OE, phosphorylation site mapping (S295), co-IP with eIF3A/eIF4B, insulin translation assay Nucleic acids research Medium 30295850
2018 DDX1 regulates alternative splicing of hundreds of target genes in pancreatic β cells (including genes associated with calcium channel function), as identified by integrated RNA-seq and CLIP-seq. Silencing DDX1 impairs calcium influx and insulin secretion. RNA-seq, CLIP-seq, DDX1 knockdown, calcium influx measurement, insulin secretion assay Biochemical and biophysical research communications Medium 29679569
2009 DDX1 is required for transcriptional activation of the cyclin-D2, CD9, and GDF3 stem cell genes in mouse spermatogonia; a genomic DDX1-binding region (-348 to -329) in the cyclin-D2 promoter was identified by reporter and gel-shift assays. DDX1-knockdown TGCT cells cannot form solid tumors in nude mice. siRNA knockdown, reporter assay, gel-shift assay (EMSA), nude mouse tumor formation, in situ hybridization Oncogene Medium 19398953
2018 DDX1 directly binds the -1837 to -1662 enhancer/promoter region of the human LGR5 gene and activates its transcription in colorectal cancer cells. DDX1 knockout (CRISPR/Cas9) reduces LGR5, CD133, ALDH1, and SOX2 expression, reduces sphere formation, and abolishes tumorigenicity in nude mice. CRISPR/Cas9 gene knockout, reporter assay, chromatin immunoprecipitation (ChIP), soft agar colony assay, nude mouse xenograft, rescue with DDX1 re-expression Cancer science Medium 29869821
2013 DDX1 regulates the subcellular localization of the ARE-binding protein KSRP; DDX1 knockdown elevates cytoplasmic KSRP, facilitates ARE-mediated mRNA decay, and increases KSRP association with 14-3-3 proteins. KSRP associates with DDX1 or 14-3-3 in a mutually exclusive manner. KSRP protein complex purification, Co-IP, DDX1 siRNA knockdown, ARE-mediated mRNA decay assay PloS one Medium 24023901
2014 DDX1 (along with HSPC117/RTCB and FAM98B) associates with hCLE/C14orf166 in both nuclear and cytoplasmic compartments and shuttles between nucleus and cytoplasm transporting RNAs. Nuclear import of the complex requires active transcription. Silencing hCLE downregulates nuclear and cytosolic accumulation of DDX1, HSPC117, and FAM98B. Co-IP of nuclear and cytoplasmic fractions, photoactivatable GFP (PAGFP) hCLE tracking, transcription inhibition, mass spectrometry of purified complexes PloS one Medium 24608264
2021 Edited Azin1 protein (AZI) translocates to the nucleus and binds DDX1 with enhanced affinity, altering the chromatin distribution of DDX1 and changing expression of hematopoietic regulators to promote HSPC differentiation. RNA editing profiling (RNA-seq), Co-IP (AZI-DDX1), chromatin fractionation, functional HSPC differentiation assays Blood Medium 34388251
2024 DDX1 physically interacts with the RNA exosome subunit EXOSC3 in neuronal cells; this interaction is decreased in the presence of DNA damage. Loss of EXOSC3 or DDX1 alters R-loop accumulation genome-wide, as shown by DRIP-seq. EXOSC3 immunoprecipitation followed by proteomics, Co-IP, DRIP-seq in N2A cells with EXOSC3 or DDX1 depletion The Journal of biological chemistry Medium 38219817
2025 EZH2 methylates DDX1 at lysine 234 (K234), promoting intervertebral disc degeneration. DDX1 K234 methylation disrupts its interaction with splicing factors and RNA targets, causing exon 14 skipping in MATR3. The truncated MATR3 disrupts nuclear architecture, increases chromatin accessibility, and activates Wnt signaling, leading to nucleus pulposus cell senescence and apoptosis. Identification by proteomics; EZH2 inhibition in vitro/in vivo; K234 methylation confirmed by mass spectrometry; RNA-seq (splicing analysis); nuclear architecture assays; ATAC-seq; lipid nanoparticle mRNA delivery rescue Nature communications Medium 40610464
2025 DDX1 is crotonylated at lysine 490 by GCN5 (crotonyltransferase); HDAC1 acts as the decrotonylase. K490 crotonylation enhances DDX1 interaction with HNRNPK, promoting mutually exclusive alternative splicing of ACOX1, which generates peroxisomal ROS and suppresses colorectal cancer cell proliferation. Mass spectrometry crotonylation profiling, GCN5/HDAC1 modulation, Co-IP (DDX1-HNRNPK), RNA-seq (ACOX1 splicing), ROS measurement, cell proliferation assays Free radical biology & medicine Medium 41197750
2023 SARS-CoV-2 nucleocapsid protein (Np) physically interacts with DDX1 and DDX3X; Np increases DDX1 protein levels. Np binding increases the affinity of DDX1 for double-stranded RNA 2- to 4-fold in a helicase-independent manner, while Np inhibits the RNA helicase activity of DDX1. Co-IP, ATPase/helicase activity assays with recombinant proteins, dsRNA binding assays International journal of molecular sciences Medium 36982856
2026 SARS-CoV-2 N protein interacts with DDX1 in a phosphorylation-dependent manner: GSK-3-mediated phosphorylation of the N protein SR region is required for DDX1 binding (demonstrated by GSK-3 inhibition, Ser-to-Ala mutants, and phospho-mimetic SR peptides). Phosphorylated SR peptides prevent and disrupt N-DDX1 complexes in vitro. The DDX1 N-terminal domain mediates this interaction. RNase treatment does not alter N-DDX1 interactions. Co-IP in HEK293 cells, GSK-3 inhibition, site-directed mutagenesis, alkaline phosphatase treatment, in vitro peptide competition assay, domain mapping The Journal of biological chemistry High 41903808
2025 USP45 deubiquitinase directly removes polyubiquitin chains from DDX1 (and RTCB), stabilizing both proteins. USP45-mediated DDX1 deubiquitination requires RTCB, but RTCB deubiquitination is DDX1-independent, revealing an asymmetric regulatory hierarchy. USP45 cooperates with DDX1 and RTCB to promote tumor proliferation and chemoresistance. Co-IP, co-localization, deubiquitination assay, substrate-specific stabilization experiments, cellular/murine tumor models International journal of biological macromolecules Medium 41468936
2025 PRMT1 methylates DDX1 at arginine 602 (R602-ADMA), promoting DDX1 nuclear localization by recruiting USP10, which deubiquitinates DDX1. Methylated DDX1 in turn transcriptionally promotes PRMT1 and USP10 by binding their mRNA 3'UTRs, establishing a positive feedback loop. A PRMT1-specific inhibitor (GSK715) suppresses CCA progression in an in situ mouse model. Proteomics + ADMA modificationomics, HPLC-MS/MS (PRMT1 as methyltransferase, USP10 as deubiquitinase identification), immunofluorescence, nuclear-cytoplasmic fractionation, RNA-seq, hydrodynamic CCA mouse model Clinical and molecular hepatology Medium 41668296
2025 TFIIH (through the CAK sub-complex) cooperates with DDX1, SFPQ, and NONO in a chromatin-bound assembly required to process R-loops formed during RNA Pol II elongation. TTD-specific variants in ERCC2/XPD destabilize TFIIH, alter the CAK–DDX1–SFPQ–NONO interaction, and cause R-loop accumulation and transcriptional stress. Mass spectrometry of chromatin-bound CAK, gene silencing (R-loop assay), immunofluorescence, TTD patient variant analysis Nucleic acids research Medium 40757642
2025 Cryo-EM structure of the human tRNA ligase complex at atomic resolution reveals that CGI-99, DDX1, and FAM98B form an alpha-helical bundle that contacts RTCB on the opposite side from the ligase active site, with DDX1 tethered to the complex via its C-terminal helix. FAM98A and FAM98C underpin compositionally distinct RTCB-containing complexes lacking Ashwin. Cryo-EM, structure-based mutagenesis, interaction analysis with mutant subunits bioRxivpreprint High bio_10.1101_2025.08.01.668197
2025 DDX1 is required for germinal center B-cell clonal expansion and affinity maturation; DDX1-deficient B-cells upregulate c-MYC upon T-follicular helper cell contact but fail to proliferate. This proliferation block correlates with reduced mRNA translation, and DDX1 promotes protein biosynthesis through modulation of tRNA ligase complex activity and tRNA splicing. B-cell-specific Ddx1 knockout, germinal center assays, mRNA translation measurement, tRNA splicing assays bioRxivpreprint Medium bio_10.1101_2025.01.10.632317
2025 DDX1 hydrolyzes only ATP and deoxy-ATP (not other NTPs) in the presence of RNA. ATPase activity is stimulated by single-stranded RNA ≥10 nt, blunt-ended dsRNA, RNA/DNA hybrids, and (to a lesser extent) single-stranded DNA. This defines the nucleotide and nucleic acid substrate specificity of DDX1. In vitro ATPase assays with defined nucleotide and nucleic acid substrates, systematic substrate panel ACS omega High 39895751
2020 Gle1 nucleocytoplasmic shuttling regulates DDX1 nuclear localization and its interaction with CstF-64 at transcription termination sites; disruption of Gle1 shuttling increases DDX1 nucleoplasmic localization, decreases DDX1–Gle1 and DDX1–CstF-64 interactions, and increases nuclear R-loop signal. Peptide-mediated disruption of Gle1 shuttling, immunofluorescence, co-IP, R-loop staining (S9.6 antibody) Molecular biology of the cell Medium 32755435

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 306 21703541
2014 Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription. Cell host & microbe 172 25299332
2018 RNA Helicase DDX1 Converts RNA G-Quadruplex Structures into R-Loops to Promote IgH Class Switch Recombination. Molecular cell 157 29731414
2002 Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 144 11850545
2014 Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors. Nature 101 24870230
2010 The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication. Journal of virology 93 20573827
2014 The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression. Cell reports 92 25176654
1995 Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma. Oncogene 87 7731693
1998 Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines. The Journal of biological chemistry 78 9694872
2001 Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA. Molecular biology of the cell 72 11598190
2005 The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes. Virology 69 15892970
2002 An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K. The Journal of biological chemistry 66 12183465
2011 DDX1 is an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. Journal of molecular biology 63 22051512
2009 The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear factor kappaB-mediated transcription. Journal of cellular biochemistry 54 19058135
2005 Dynamic nature of cleavage bodies and their spatial relationship to DDX1 bodies, Cajal bodies, and gems. Molecular biology of the cell 54 16371507
1996 Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group. Oncogene 54 8622876
2014 hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel transcription-dependent shuttling RNA-transporting complex. PloS one 52 24608264
2009 DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes. Oncogene 49 19398953
2017 Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production. Frontiers in immunology 46 28848548
2011 Single-molecule studies reveal that DEAD box protein DDX1 promotes oligomerization of HIV-1 Rev on the Rev response element. Journal of molecular biology 46 21763499
1996 The DDX1 gene maps within 400 kbp 5' to MYCN and is frequently coamplified in human neuroblastoma. Genes, chromosomes & cancer 43 8834178
2004 Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 40 15226335
2021 A comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation. Blood 36 34388251
2016 FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved in colorectal cancer progression. The international journal of biochemistry & cell biology 33 28040436
2016 Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells. Antiviral research 32 27105836
2018 RNA-binding protein DDX1 is responsible for fatty acid-mediated repression of insulin translation. Nucleic acids research 31 30295850
2018 DEAD box protein DDX1 promotes colorectal tumorigenesis through transcriptional activation of the LGR5 gene. Cancer science 28 29869821
2014 A HIV-1 Tat mutant protein disrupts HIV-1 Rev function by targeting the DEAD-box RNA helicase DDX1. Retrovirology 28 25496916
2001 Amplification of Mycn, Ddx1, Rrm2, and Odc1 in rat uterine endometrial carcinomas. Genes, chromosomes & cancer 26 11433525
2015 Ddx1 knockout results in transgenerational wild-type lethality in mice. Scientific reports 24 25909345
2022 DEAD box 1 (DDX1) protein binds to and protects cytoplasmic stress response mRNAs in cells exposed to oxidative stress. The Journal of biological chemistry 23 35752363
2021 Chicken DDX1 Acts as an RNA Sensor to Mediate IFN-β Signaling Pathway Activation in Antiviral Innate Immunity. Frontiers in immunology 23 34630423
2019 The DEAD-Box RNA Helicase DDX1 Interacts with the Viral Protein 3D and Inhibits Foot-and-Mouth Disease Virus Replication. Virologica Sinica 23 31359346
2015 Synergistic effects of ATP and RNA binding to human DEAD-box protein DDX1. Nucleic acids research 23 25690890
2007 DDX1 promotes proliferation of the JC virus through transactivation of its promoter. Microbiology and immunology 23 17380054
2021 A novel all-in-one conditional knockout system uncovered an essential role of DDX1 in ribosomal RNA processing. Nucleic acids research 21 33503245
1996 Amplification of a DEAD box gene (DDX1) with the MYCN gene in neuroblastomas as a result of cosegregation of sequences flanking the MYCN locus. Genes, chromosomes & cancer 21 8834177
2019 hCLE/RTRAF-HSPC117-DDX1-FAM98B: A New Cap-Binding Complex That Activates mRNA Translation. Frontiers in physiology 20 30833903
2007 Identification of DDX1 as a JC virus transcriptional control region-binding protein. Microbiology and immunology 19 17380053
2017 Role for RIF1-interacting partner DDX1 in BLM recruitment to DNA double-strand breaks. DNA repair 18 28544931
1996 Physical mapping of the DDX1 gene to 340 kb 5' of MYCN. Oncogene 18 8875996
2018 DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells. Biochemical and biophysical research communications 17 29679569
2023 Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA. International journal of molecular sciences 16 36982856
2015 Loss of the Drosophila melanogaster DEAD box protein Ddx1 leads to reduced size and aberrant gametogenesis. Developmental biology 16 26433063
2002 Reduced levels of DEAD-box proteins DBP-RB and p72 in fetal Down syndrome brains. Neurochemical research 16 12462412
2019 Cytoplasmic aggregation of DDX1 in developing embryos: Early embryonic lethality associated with Ddx1 knockout. Developmental biology 15 31330130
2015 Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein. Acta crystallographica. Section F, Structural biology communications 15 26323305
2024 The putative RNA helicase DDX1 associates with the nuclear RNA exosome and modulates RNA/DNA hybrids (R-loops). The Journal of biological chemistry 14 38219817
2013 Involvement of germline DDX1-MYCN duplication in inherited nephroblastoma. European journal of medical genetics 13 24161495
2023 Depleting DDX1 sensitizes non-small cell lung cancer cells to chemotherapy by attenuating cancer stem cell traits. Life sciences 12 36934972
2022 Knockdown of ZBTB11 impedes R-loop elimination and increases the sensitivity to cisplatin by inhibiting DDX1 transcription in bladder cancer. Cell proliferation 12 36054300
2002 Cloning and expression analysis of the chicken DEAD box gene DDX1. Biochimica et biophysica acta 12 11955614
2021 DDX1 from Cherry valley duck mediates signaling pathways and anti-NDRV activity. Veterinary research 11 33472667
2013 DEAD box protein DDX1 regulates cytoplasmic localization of KSRP. PloS one 11 24023901
2025 DDX1 methylation mediated MATR3 splicing regulates intervertebral disc degeneration by initiating chromatin reprogramming. Nature communications 9 40610464
2022 DDX1 vesicles control calcium-dependent mitochondrial activity in mouse embryos. Nature communications 8 35778392
2007 Concomitant DDX1 and MYCN gain in neuroblastoma. Cancer letters 8 17611020
1996 A Drosophila melanogaster homologue of the human DEAD-box gene DDX1. Gene 8 8666277
2025 Substrate Specificities of DDX1: A Human DEAD-Box Protein. ACS omega 6 39895751
2025 DDX1 is required for non-spliceosomal splicing of tRNAs but not of XBP1 mRNA. Communications biology 5 39833356
2023 The RNA-Splicing Ligase RTCB Promotes Influenza A Virus Replication by Suppressing Innate Immunity via Interaction with RNA Helicase DDX1. Journal of immunology (Baltimore, Md. : 1950) 5 37556111
2020 Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites. Molecular biology of the cell 4 32755435
2024 Substrate Specificities of DDX1: A Human DEAD-box protein. bioRxiv : the preprint server for biology 3 38260591
2023 Role of DDX1 in the oxidative response of ataxia telangiectasia patient-derived fibroblasts. Redox biology 3 38096740
2025 Trichothiodystrophy-causative pathogenic variants impair a cooperative action of TFIIH and DDX1 in R-loop processing. Nucleic acids research 2 40757642
2024 CircInpp5b Ameliorates Renal Interstitial Fibrosis by Promoting the Lysosomal Degradation of DDX1. Biomolecules 2 38927017
1999 Expression of two dead box genes (DDX1 and DDX6) is independent of that of MYCN in human neuroblastoma cell lines. Biochemistry and molecular biology international 2 10319407
2025 DDX1 crotonylation mediates ACOX1 alternative splicing through HNRNPK to increase peroxisomal oxidative damage. Free radical biology & medicine 1 41197750
2025 Deubiquitinase USP45 stabilizes RTCB and DDX1, promoting tumorigenesis and chemoresistance. International journal of biological macromolecules 1 41468936
2023 The RNA helicase DDX1 associates with the nuclear RNA exosome and modulates R-loops. bioRxiv : the preprint server for biology 1 37131662
2026 PRMT1-mediated asymmetric dimethylation of arginine residue 602 in DDX1 promotes cholangiocarcinoma progression. Clinical and molecular hepatology 0 41668296
2026 Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5. European journal of medicinal chemistry 0 41795418
2026 Direct interaction between human DDX1 and SARS-CoV-2 nucleocapsid protein is regulated by phosphorylation. The Journal of biological chemistry 0 41903808
2026 ACOD1 deficiency promotes DDX1 methylation-mediated mitochondrial dysfunction and dermal papilla cell senescence in androgenetic alopecia. BMC medicine 0 42218500
2025 DDX1 facilitates lenvatinib resistance in hepatocellular carcinoma through regulating ephrin-A3 and activating the Wnt/β-catenin signaling pathway. Functional & integrative genomics 0 41186842
2023 Phosphorylation impacts GLE1 nuclear localization and association with DDX1. Advances in biological regulation 0 37801910

Missed literature

Know a paper Affinage missed for DDX1? Flag it for the maintainers and the community.

No submissions yet.