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-Structure paper
| タイトル | Human DHX29 detects nonoptimal codon usage to regulate mRNA stability. |
|---|---|
| ジャーナル・号・ページ | Science, Vol. 392, Issue 6798, Page eadw0288, Year 2026 |
| 掲載日 | 2026年5月7日 |
著者 | Fabian 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 要旨 | Synonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Nonoptimal codons are known to induce messenger RNA (mRNA) decay; however, the underlying molecular ...Synonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Nonoptimal codons are known to induce messenger RNA (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. Cryo-electron microscopy and selective ribosome profiling demonstrated that DHX29 directly interacts with the A-site entrance of the translating 80 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. |
リンク | Science / PubMed:41855277 |
| 手法 | EM (単粒子) |
| 解像度 | 3.0 Å |
| 構造データ | EMDB-68666, PDB-22tu: |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-ZN: |
| 由来 |
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キーワード | TRANSLATION / ribosome |
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homo sapiens (ヒト)
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