22tu
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Human 80S ribosome in complex with DHX29
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Structural highlights
FunctionPublication Abstract from PubMedSynonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Nonoptimal 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 nonoptimal mRNAs. These findings establish a mechanistic link between synonymous codon usage and the regulation of gene expression. Human DHX29 detects nonoptimal codon usage to regulate mRNA stability.,Hia F, Wu Y, Yoshinaga M, Goto-Ito S, Iwasaki W, Imami K, Toh H, Han P, Cai T, Ohira T, Fukao A, Standley DM, Shichino Y, Takegawa M, Fujiwara T, Suzuki T, Iwasaki S, Bassik MC, Ito T, Takeuchi O Science. 2026 Mar 19:eadw0288. doi: 10.1126/science.adw0288. PMID:41855277[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 15:47, 1 April 2026.