Medulloblastoma-associated mutations in the RNA helicase DDX3X/DED1 cause defects in the translational response to TORC1 inhibition

Swarup A, Kuhs RA, Hardman VU, Howard KL, Subbaraman S, Bolger TA · 2026 · The Journal of Biological Chemistry · Atlas ID SWA2026

What this study shows

Medulloblastoma-associated DDX3X mutations, modeled in the yeast ortholog Ded1 (ded1-mam), cause rapamycin-resistant growth and selectively upregulate translation of unstructured-5'UTR pro-growth transcripts after TORC1 inhibition, a mechanism by which mutant DDX3X may let tumor cells bypass TORC1-dependent stress/growth control.

Abstract

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Medulloblastoma is the most common pediatric brain cancer, but current treatments are largely non-specific, often causing developmental side effects. Genomic sequencing identified the RNA helicase DDX3X as one of the most frequently mutated genes in this cancer and a potential treatment target, yet its role in tumor progression remains elusive.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Saccharomyces cerevisiae (ded1-mam mutant) and medulloblastoma-relevant reporter assays) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Saccharomyces cerevisiae (ded1-mam mutant) and medulloblastoma-relevant reporter assays
Journal	The Journal of Biological Chemistry
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.jbc.2026.113580 · PMID 42759659

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	rapamycin (TOR inactivation) in yeast carrying medulloblastoma-associated ded1-mam mutations; 5' UTR reporter assays
Target	TORC1-dependent translational control via the RNA helicase Ded1 / DDX3X
Model	Saccharomyces cerevisiae with medulloblastoma-relevant reporter assays
Effect	The mutant grew substantially better than wild type under rapamycin and selectively raised translation of unstructured-5'UTR transcripts after TOR inhibition, rather than raising bulk translation.

In the Atlas

Cite this paper

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Swarup, A., Kuhs, R. A., Hardman, V. U., Howard, K. L., Subbaraman, S., & Bolger, T. A. (2026). Medulloblastoma-associated mutations in the RNA helicase DDX3X/DED1 cause defects in the translational response to TORC1 inhibition. The Journal of Biological Chemistry. https://doi.org/10.1016/j.jbc.2026.113580

@article{SWA2026,
  author       = {Swarup, A. and Kuhs, R. A. and Hardman, V. U. and Howard, K. L. and Subbaraman, S. and Bolger, T. A.},
  title        = {{Medulloblastoma-associated mutations in the RNA helicase DDX3X/DED1 cause defects in the translational response to TORC1 inhibition}},
  journal      = {The Journal of Biological Chemistry},
  year         = {2026},
  doi          = {10.1016/j.jbc.2026.113580},
  note         = {PMID: 42759659},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SWA2026) [Data set]. https://mtor-atlas.org/study/SWA2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SWA2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SWA2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SWA2026/},
  doi          = {10.5281/zenodo.22059963}
}

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