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TitleHuman DHX29 detects nonoptimal codon usage to regulate mRNA stability.
Journal, issue, pagesScience, Page eadw0288, Year 2026
Publish dateMar 19, 2026
AuthorsFabian Hia / Yitong Wu / Masanori Yoshinaga / Sakurako Goto-Ito / Wakana Iwasaki / Koshi Imami / Hirotaka Toh / Peixun Han / Ting Cai / Takayuki Ohira / Akira Fukao / Daron M Standley / Yuichi Shichino / Masaki Takegawa / Toshinobu Fujiwara / Tsutomu Suzuki / Shintaro Iwasaki / Michael C Bassik / Takuhiro Ito / Osamu Takeuchi /
PubMed AbstractSynonymous 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 ...Synonymous 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.
External linksScience / PubMed:41855277
MethodsEM (single particle)
Resolution3.0 Å
Structure data

68666

22tu

EMDB-68666, PDB-22tu:
Human 80S ribosome in complex with DHX29
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsTRANSLATION / ribosome

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