DHX29 Detects Non-Optimal Codons to Control Gene Expression
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- DHX29 protein detects and suppresses mRNAs containing non-optimal codons, revealing a hidden layer of gene regulation beyond the traditional genetic code.
- Kyoto University and RIKEN researchers (led by Osamu Takeuchi and Takuhiro Ito) identified DHX29 via genome-wide CRISPR screening; RNA sequencing confirmed mRNAs with non-optimal codons accumulate when DHX29 is absent.
- Cryo-electron microscopy revealed DHX29 physically binds the 80S ribosome, with selective ribosome profiling showing it preferentially associates with ribosomes reading weaker codons.
- The study found DHX29 recruits the GIGYF2•4EHP protein complex, which selectively suppresses mRNAs with non-optimal codons and reduces production of inefficient genetic messages.
- Co-corresponding author Masanori Yoshinaga said the findings reveal "a direct molecular link between synonymous codon choice and the control of gene expression in human cells."
- Published in Science (2026, DOI: 10.1126/science.adw0288), the research team says the mechanism could influence cell differentiation, cellular balance, and cancer development.
Why it matters: Synonymous codons long treated as redundant now have a concrete mechanism: the protein DHX29, working with the GIGYF2•4EHP complex, actively silences mRNAs carrying weaker instructions. Researchers studying cell differentiation and cancer biology gain a direct molecular handle on how codon-level choices shape gene expression in human cells.
