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Showing DDX52ROK1 is a alias.

DDX52

Probable ATP-dependent RNA helicase DDX52 · UniProt Q9Y2R4

Length
599 aa
Mass
67.5 kDa
Annotated
2026-06-09
18 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX52 (yeast Rok1) is an essential ATP-dependent DEAD-box RNA helicase that drives remodeling of pre-ribosomal complexes during small-subunit biogenesis (PMID:8529880, PMID:10373593, PMID:18833290). Its intrinsic ATPase activity is RNA-independent in vitro, and mutation of conserved ATPase motifs abolishes catalysis and causes lethality, establishing ATP hydrolysis as the core of its function (PMID:10373593). Mechanistically, Rok1 is specifically required to release the essential snoRNA snR30 from pre-ribosomes, with distinct helicase motifs contributing unequally to this step, and it directly cross-links to pre-rRNA at expansion segment ES6 in the 'foot' of the small subunit where snR30 base-pairs (PMID:18833290, PMID:24947498). Nucleotide state couples this remodeling to the cofactor Rrp5: ATP-bound Rok1 stabilizes Rrp5 on pre-40S ribosomes while ATP hydrolysis releases Rrp5 to permit 60S assembly, and Rok1 is also required for accurate Rrp5 positioning in the nucleolus (PMID:27280440, PMID:35628496). The ribosome-biogenesis role is conserved across species, supporting 47S pre-rRNA maintenance and growth in zebrafish and pre-rRNA processing with mitotic progression in Drosophila (PMID:34323273, PMID:35628496). Human DDX52 acts as an ATP-dependent 3'-to-5' translocase that unwinds DNA duplexes and DNA/RNA hybrids and, conversely, possesses an annealase activity that depends on its N-terminal intrinsically disordered region and is hyperactive when helicase activity is disabled (PMID:41510705). In human cancer cells, DDX52 physically associates with c-Myc mRNA and supports c-Myc-dependent oncogenic signaling, with knockdown suppressing tumor growth (PMID:34233596).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 Medium

    Established that ROK1 encodes an essential DEAD-box helicase, placing it in the ATP-dependent RNA helicase class before any biochemical activity was known.

    Evidence Sequence analysis and genetic suppressor screen of the kem1 null in yeast

    PMID:8529880

    Open questions at the time
    • No enzymatic activity demonstrated
    • No substrate or pathway assigned
    • Functional link to kem1 mechanism unresolved
  2. 1998 Medium

    Determined the subcellular distribution of Rok1, providing the first spatial context for its activity.

    Evidence Indirect immunofluorescence with affinity-purified anti-Rok1 antibodies in S. cerevisiae

    PMID:9571634

    Open questions at the time
    • Single localization method, no functional consequence
    • Cytoplasmic signal does not address nucleolar pool seen in later orthologs
  3. 1999 High

    Showed that ATP hydrolysis is the essential catalytic core of Rok1 function, and unexpectedly that its ATPase is RNA-independent in vitro.

    Evidence In vitro ATPase assay with purified MBP-Rok1, ATPase-motif mutagenesis, and in vivo lethality tests

    PMID:10373593

    Open questions at the time
    • RNA substrate that activates ATPase in vivo not identified
    • No structural basis for RNA-independence
  4. 2008 High

    Pinpointed Rok1's specific substrate step in ribosome assembly—release of snR30—and revealed functional non-equivalence among helicase motifs.

    Evidence Quantitative snoRNA-association screen across 75 snoRNAs with motif I/III point mutants in yeast depletion strains

    PMID:18833290

    Open questions at the time
    • Direct rRNA contact site not yet mapped
    • Whether release is direct unwinding or remodeling unclear
  5. 2014 High

    Localized Rok1's direct pre-rRNA contacts to expansion segment ES6 in the subunit foot, providing nucleotide-resolution evidence for where it acts on snR30.

    Evidence CRAC and CLASH UV cross-linking mapping in yeast

    PMID:24947498

    Open questions at the time
    • Does not establish catalytic order relative to Rrp5
    • Functional consequence of each cross-link site untested
  6. 2016 High

    Defined a nucleotide-state cycle in which ATP-bound Rok1 stabilizes Rrp5 and hydrolysis releases it, mechanistically coupling 40S remodeling to downstream 60S assembly.

    Evidence In vitro ATP/ADP-form binding assays, Rrp5 co-IP, and in vivo functional epistasis in yeast

    PMID:27280440

    Open questions at the time
    • Structural model of the Rok1-Rrp5-pre40S complex absent
    • Trigger for ATP hydrolysis in vivo unknown
  7. 2021 Medium

    Demonstrated conservation of the ribosome-biogenesis role in a vertebrate, linking DDX52 to 47S pre-rRNA maintenance and organismal growth.

    Evidence Forward genetic screen, positional cloning, and 47S pre-rRNA quantification in zebrafish

    PMID:34323273

    Open questions at the time
    • Molecular step in vertebrate processing not resolved
    • snR30 ortholog dependence not tested
  8. 2021 Medium

    Connected DDX52 to c-Myc oncogenic signaling, including direct binding to c-Myc mRNA, extending its biology to cancer cell proliferation.

    Evidence shRNA knockdown, RNA immunoprecipitation, xenografts, and c-Myc rescue in melanoma and prostate cancer cells

    PMID:34233596 PMID:34399732

    Open questions at the time
    • Whether c-Myc mRNA effect is via helicase activity untested
    • Relationship to ribosome biogenesis role in tumors unclear
    • c-Myc transcriptional feedback inferred from knockdown only
  9. 2022 Medium

    Confirmed nucleolar co-localization and co-dependence of Rok1 and Rrp5 in a multicellular animal and tied Rok1 loss to mitotic arrest, reinforcing the conserved assembly mechanism.

    Evidence Drosophila mutant genetics, FISH, and developmental phenotyping

    PMID:35628496

    Open questions at the time
    • Mitotic defect may be indirect consequence of stalled biogenesis
    • Direct Rrp5 interaction not biochemically shown in fly
  10. 2026 High

    Resolved the human enzyme's biochemical repertoire, showing it is a 3'-5' translocase that unwinds DNA and DNA/RNA hybrids and also anneals strands via its N-terminal IDR, expanding its activity beyond canonical RNA remodeling.

    Evidence In vitro helicase/translocase and annealing assays, helicase-dead mutagenesis, and CRISPR heterozygous knockout phenotyping in U2OS cells

    PMID:41510705

    Open questions at the time
    • Physiological substrate of DNA/hybrid unwinding unknown
    • How annealase vs helicase activity is regulated in cells unresolved
    • Link between in vitro activities and migration/growth phenotype not established
  11. 2026 Low

    Implicated Rok1 in cytokinesis and chromosome segregation in fission yeast through transcriptomic effectors, broadening its phenotypic footprint.

    Evidence Live-cell imaging of actin ring and kinetochores plus RNA sequencing in S. pombe rok1 deletion

    PMID:42016605

    Open questions at the time
    • Downstream effectors inferred from transcriptomics without rescue validation
    • Direct mechanistic link to helicase activity not established
    • May reflect indirect consequence of ribosome biogenesis defect

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DDX52's biochemically defined DNA/RNA unwinding and annealase activities relate mechanistically to its established role in pre-ribosome remodeling and to c-Myc-dependent oncogenesis remains unresolved.
  • No physiological substrate linking helicase/annealase activities to ribosome assembly
  • No structural model of the human enzyme on substrate
  • Mechanism connecting DDX52 to c-Myc mRNA fate undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0140657 ATP-dependent activity 3 GO:0140098 catalytic activity, acting on RNA 2 GO:0003677 DNA binding 1 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
Complex memberships
pre-40S ribosome

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 ROK1 encodes an essential yeast protein containing conserved DEAD-box domains characteristic of ATP-dependent RNA helicases; it was identified as a high-copy suppressor of the kem1 null mutation. Sequence analysis, genetic suppressor screen, viability assays Gene Medium 8529880
1998 Rok1 protein (~64 kDa) is localized predominantly to the cytoplasm in vegetatively growing Saccharomyces cerevisiae cells, as determined by indirect immunofluorescence with affinity-purified anti-Rok1 antibodies. Western blot, indirect immunofluorescence Molecules and cells Medium 9571634
1999 Rok1 possesses intrinsic ATPase activity, and mutations in conserved ATPase motifs abolish this activity and cause in vivo lethality, demonstrating that ATP hydrolysis is essential for Rok1 function. Notably, the ATPase activity is RNA-independent. In vitro ATPase assay with purified MBP-Rok1 fusion protein, site-directed mutagenesis, in vivo lethality tests Nucleic acids research High 10373593
2008 The DEAD-box helicase Rok1 is specifically required for release of the essential snoRNA snR30 from pre-ribosomes during 40S subunit synthesis. Point mutations in helicase motif I impair snR30 release, while motif III mutations do not, indicating mechanistic specificity of different helicase motifs. Quantitative snoRNA association screen (Northern blot-based), helicase domain point mutations, yeast depletion strains EMBO reports High 18833290
2010 Rok1 protein levels oscillate during the yeast cell cycle (declining at G1/S, increasing at G2), controlled by two upstream open reading frames (uORFs) in the ROK1 5'-UTR that inhibit translation. Disrupting uORFs elevates Rok1 levels and causes delays in bud emergence and recovery from pheromone arrest. uORF mutagenesis, Western blot cell-cycle analysis, pheromone arrest/release assays FEBS letters Medium 20969870
2014 UV cross-linking (CRAC) revealed that Rok1 directly contacts pre-rRNA at multiple sites clustering in the 'foot' region of the small ribosomal subunit, particularly the expansion segment ES6, where it promotes snR30 release. CLASH further identified novel pre-rRNA base-pairing sites for snR30, snR10, U3, and U14 clustering in expansion segments, suggesting these snoRNAs bridge long-range rRNA interactions during early ribosome assembly. UV cross-linking and analysis of cDNA (CRAC), cross-linking ligation and sequencing of hybrids (CLASH) RNA (New York, N.Y.) High 24947498
2015 Three ROK1 5'-UTR-binding proteins—Psk2 (PAS kinase), Skp1, and Tub4—regulate Rok1 translation through uORF1: Psk2 and Skp1 repress Rok1 synthesis, while Tub4 promotes it, acting downstream of uORF1-mediated inhibition. Yeast three-hybrid screening, PSK2 deletion analysis, temperature-sensitive alleles of SKP1 and TUB4 Journal of microbiology (Seoul, Korea) Medium 26310304
2016 ATP-bound (but not ADP-bound) Rok1 stabilizes Rrp5 binding to pre-40S ribosomes, and ATP hydrolysis by Rok1 is required to release Rrp5 from pre-40S ribosomes in vivo, freeing Rrp5 to participate in 60S subunit assembly. Blocked Rrp5 release causes secondary accumulation of snR30. An interaction between Rrp5 and the DEAD-box protein Has1 is implicated in snR30 accumulation when Rrp5 release is blocked. In vivo and in vitro biochemical analyses, ATP/ADP-form Rok1 binding assays, Rrp5 co-immunoprecipitation, functional epistasis PLoS biology High 27280440
2021 Ddx52 (the zebrafish ortholog of DDX52) maintains the level of 47S precursor ribosomal RNA and is essential for juvenile growth; loss-of-function by temperature-sensitive mutation suspends whole-organism growth reversibly. Forward genetic screen, positional cloning, complementation assays, 47S pre-rRNA quantification Development (Cambridge, England) Medium 34323273
2021 DDX52 knockdown in prostate cancer cells inhibits cell growth in vitro and in vivo, and suppresses c-Myc signaling; conversely, c-Myc transcriptionally regulates DDX52 expression, forming a positive feedback loop. shRNA knockdown, RNA sequencing, GSEA, Western blot, xenograft mouse model, IHC Cancer cell international Low 34399732
2021 DDX52 knockdown suppresses melanoma cell proliferation and tumor growth, and an RNA immunoprecipitation assay confirmed physical association between DDX52 protein and c-Myc mRNA; restoration of c-Myc partly rescues DDX52-deficiency phenotypes. shRNA knockdown, RNA immunoprecipitation (RIP), xenograft mouse model, rescue assay Bioengineered Medium 34233596
2022 In Drosophila, Rok1 and its cofactor Rrp5 co-localize to the nucleolus and are both required for pre-rRNA processing and ribosome assembly. Loss of Rok1 causes nucleolar enlargement, stalled ribosome assembly, and inhibition of mitosis in the brain. Rok1 depletion also mislocalizes Rrp5 within the nucleolus, suggesting Rok1 is required for accurate Rrp5 positioning. Genetics (mutant analysis), fluorescence in situ hybridization (FISH), developmental phenotype assays International journal of molecular sciences Medium 35628496
2026 Human DDX52 is an ATP-dependent 3'-to-5' translocase/helicase that can unwind DNA duplexes and DNA/RNA hybrids in vitro. DDX52 also functions as a nucleic acid annealase (strand annealing), an activity that requires the N-terminal intrinsically disordered region (IDR) and becomes hyperactive when helicase activity is abolished by mutagenesis. CRISPR-generated DDX52+/- U2OS cells exhibit growth defects and impaired cell migration. In vitro helicase/translocase assay, strand-annealing assay, helicase-dead mutagenesis, CRISPR-Cas9 heterozygous knockout, cell migration assay Bioscience reports High 41510705
2026 In fission yeast, rok1 deletion shortens and slows actin ring contraction during cytokinesis and inhibits kinetochore separation during mitosis. Transcriptomic analysis identified upregulation of myo51 and blt1 (delaying actin ring assembly) and psm3/psc3 cohesin subunits as key downstream effectors of Rok1 deletion phenotypes. Fluorescent protein labeling, live-cell imaging, RNA sequencing, bioinformatics Experimental and therapeutic medicine Low 42016605

Source papers

Stage 0 corpus · 18 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Quantitative analysis of snoRNA association with pre-ribosomes and release of snR30 by Rok1 helicase. EMBO reports 65 18833290
2014 A pre-ribosomal RNA interaction network involving snoRNAs and the Rok1 helicase. RNA (New York, N.Y.) 42 24947498
2016 The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation. PLoS biology 38 27280440
2009 The dual specificity phosphatase Rok1 negatively regulates mating and pathogenicity in Ustilago maydis. Molecular microbiology 30 19486294
1999 ATP hydrolysis activity of the DEAD box protein Rok1p is required for in vivo ROK1 function. Nucleic acids research 23 10373593
1995 ROK1, a high-copy-number plasmid suppressor of kem1, encodes a putative ATP-dependent RNA helicase in Saccharomyces cerevisiae. Gene 23 8529880
2021 The RNA helicase Ddx52 functions as a growth switch in juvenile zebrafish. Development (Cambridge, England) 11 34323273
2010 Upstream open reading frames regulate the cell cycle-dependent expression of the RNA helicase Rok1 in Saccharomyces cerevisiae. FEBS letters 10 20969870
2021 DDX52 knockdown inhibits the growth of prostate cancer cells by regulating c-Myc signaling. Cancer cell international 9 34399732
2019 The Unfolded Protein Response Regulates Pathogenic Development of Ustilago maydis by Rok1-Dependent Inhibition of Mating-Type Signaling. mBio 9 31848283
2017 Characterization of the Es-DDX52 involved in the spermatogonial mitosis and spermatid differentiation in Chinese mitten crab (Eriocheir sinensis). Gene 8 29288727
2021 Knockdown of DEAD-box RNA helicase 52 (DDX52) suppresses the proliferation of melanoma cells in vitro and of nude mouse xenografts by targeting c-Myc. Bioengineered 7 34233596
2000 Identification of a putative DEAD-box RNA helicase and a zinc-finger protein in Candida albicans by functional complementation of the S. cerevisiae rok1 mutation. Yeast (Chichester, England) 7 10705369
2015 Identification of Psk2, Skp1, and Tub4 as trans-acting factors for uORF-containing ROK1 mRNA in Saccharomyces cerevisiae. Journal of microbiology (Seoul, Korea) 4 26310304
1998 Characterization and intracellular localization of the Rok1 protein involved in yeast cell division. Molecules and cells 4 9571634
2022 The DEAD-Box Protein Rok1 Coordinates Ribosomal RNA Processing in Association with Rrp5 in Drosophila. International journal of molecular sciences 1 35628496
2026 The human DDX52 protein is a nucleic acid helicase and strand annealase that promotes cell migration. Bioscience reports 0 41510705
2026 Effects of rok1 gene deletion on mitosis in fission yeast at appropriate and stressful temperatures and the molecular mechanisms. Experimental and therapeutic medicine 0 42016605

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