Evidence map›Paper›PMID 25724843›Full record

ArticleJournal of molecular biology2015

Cancer-associated mutants of RNA helicase DDX3X are defective in RNA-stimulated ATP hydrolysis.

Leslie B Epling, Christy R Grace, Brandon R Lowe, Janet F Partridge, Eric J Enemark

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Leslie B Epling *Department of Structural Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 311, Memphis, TN 38105, USA.
Christy R Grace *Department of Structural Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 311, Memphis, TN 38105, USA.
Brandon R Lowe *Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 350, Memphis, TN 38105, USA.
Janet F PartridgeDepartment of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 350, Memphis, TN 38105, USA.
Eric J EnemarkDepartment of Structural Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 311, Memphis, TN 38105, USA.
University of Tennessee Health Science Center · USSt. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
NCI NIH HHS 2 P30 CA21765NCI NIH HHS 5 P30 CA021765-32NCI NIH HHS P30 CA021765
6 · The paper itself

Abstract

The DEAD-box RNA helicase DDX3X is frequently mutated in pediatric medulloblastoma. We dissect how these mutants affect DDX3X function with structural, biochemical, and genetic experiments. We identify an N-terminal extension ("ATP-binding loop", ABL) that is critical for the stimulation of ATP hydrolysis by RNA. We present crystal structures suggesting that the ABL interacts dynamically with ATP and confirming that the interaction occurs in solution by NMR chemical shift perturbation and isothermal titration calorimetry. DEAD-box helicases require interaction between two conserved RecA-like helicase domains, D1 and D2 for function. We use NMR chemical shift perturbation to show that DDX3X interacts specifically with double-stranded RNA through its D1 domain, with contact mediated by residues G302 and G325. Mutants of these residues, G302V and G325E, are associated with pediatric medulloblastoma. These mutants are defective in RNA-stimulated ATP hydrolysis. We show that DDX3X complements the growth defect in a ded1 temperature-sensitive strain of Schizosaccharomyces pombe, but the cancer-associated mutants G302V and G325E do not complement and exhibit protein expression defects. Taken together, our results suggest that impaired translation of important mRNA targets by mutant DDX3X represents a key step in the development of medulloblastoma.

Indexed as

Adenosine TriphosphateBinding SitesCerebellar NeoplasmsChildCrystallizationCrystallography, X-RayDEAD-box RNA HelicasesGenetic Complementation TestHumansHydrolysisMedulloblastomaModels, MolecularMutagenesis, Site-DirectedMutationNuclear Magnetic Resonance, BiomolecularProtein BiosynthesisAdenosine TriphosphateDDX3X protein, humanDEAD-box RNA HelicasesRNAbiochemistrycrystallographygeneticsNMR

Identifiers

PMID25724843
PMCPMC4402148
OpenAlexW2013564673

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.