Most amino acids can be encoded by multiple synonymous codons. The authors report that cells distinguish “optimal” and “nonoptimal” codons in ways that affect how long an mRNA persists and how efficiently it is translated.
Using genome-wide CRISPR screening, the team identified DHX29 as a factor associated with turnover of poorly translated transcripts. Loss of DHX29 was linked to accumulation of unstable mRNAs, consistent with a role in quality control during translation.
Cryo–electron microscopy indicated that DHX29 associates with the ribosome near the peptidyl transferase centre. The authors propose that pausing at nonoptimal codons allows DHX29 to recruit a GIGYF2–4EHP complex that contributes to silencing and degradation of the affected message.
The original report includes schematic figures illustrating ribosome-associated DHX29 function. Those figures are not reproduced here; see the full paper in Science for authoritative illustrations (© American Association for the Advancement of Science).
The paper discusses how codon usage may influence mRNA stability across the transcriptome and notes possible relevance to disease biology. The authors describe DHX29 as providing a mechanistic link between codon optimality and gene expression.
For experimental details and conclusions, see the full report in Science (doi:10.1126/science.adw0288).