2026-03-23 京都大学
ヒト細胞におけるDHX29を介した非最適コドンの認識と制御
＜関連情報＞
- https://www.kyoto-u.ac.jp/ja/research-news/2026-03-23
- https://www.kyoto-u.ac.jp/sites/default/files/2026-03/web_2603_Yoshinaga-c86916e81e7b23645a6766e8e959e265.pdf
- https://www.science.org/doi/10.1126/science.adw0288
ヒト DHX29 は非最適コドンを認識しmRNA分解を制御する Human DHX29 detects nonoptimal codon usage to regulate mRNA stability
Fabian Hia, Yitong Wu, Masanori Yoshinaga, Sakurako Goto-Ito, […] , and Osamu Takeuchi
Science Published:19 Mar 2026
DOI:https://doi.org/10.1126/science.adw0288
Abstract
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.
