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Effect of DHX29 depletion on gene expression in K562 cells

GSE265999 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2026/03/19 Platform GPL18573
Summary
Synonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Non-optimal codons are known to induce mRNA decay; however, the underlying molecular mechanism remains poorly understood in human cells. Through genome-wide CRISPR screening, we identified the RNA-binding protein DHX29 as a critical regulator of codon-dependent gene expression. Cryogenic electron microscopy and selective ribosome profiling demonstrated that DHX29 directly interacts with the A-site entrance of the translating 80S ribosome, the binding site for the eEF1A•GTP•aminoacyl-tRNA ternary complex, suggesting a role in monitoring aminoacyl-tRNA sampling. Proteomic analysis further revealed that DHX29 recruits the GIGYF2•4EHP complex to mediate global suppression of non-optimal mRNAs. These findings establish a mechanistic link between synonymous codon usage and the regulation of gene expression.
Published in
Human DHX29 detects nonoptimal codon usage to regulate mRNA stability
Hia F, Wu Y, Yoshinaga M et al. · Science (New York, N.Y.) 2026 · PMID 41855277 · doi:10.1126/science.adw0288
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Also filed as BioProject PRJNA1105109 and SRA study SRP504291. Searching any of these in the dataset finder brings you back here.

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