The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality

Recent experimental findings have substantially advanced the notion that the codon-dependent rate of translation elongation is a major determinant of mRNA stability. While the role of the ribosome in identification and decay of aberrant mRNAs has been well established, how the process of translation elongation and mRNA decay communicate is less well understood. Here, we report that the yeast DEAD-box protein Dhh1, long implicated in regulation of translation and activation of mRNA decay, acts as a sensor of codon optimality that targets an mRNA for decay. First, we find that Dhh1 specifically associates with and degrades mRNAs of low codon optimality. We show that messages with greater numbers of slowly translating ribosomes are preferential targets for Dhh1 mediated decay. Moreover, we note that these mRNAs are degraded by Dhh1-specific mechanism separate from the standard cellular ribosome quality control apparatus. We find that overexpression of Dhh1 leads to accumulation of ribosomes specifically on mRNAs of poor optimality. We supplement this with high-throughput sequencing analysis to show that Dhh1 over-expression leads to ribosomal stalling on specific non-optimal codons. Taken together with the finding that Dhh1 is found to associate with ribosomes in vivo, these data suggest that Dhh1 acts a sensor for translation elongation, efficiently coupling codon optimality with mRNA decay