Combinations of slow-translating codon clusters can increase mRNA half-life in <i>Saccharomyces cerevisiae</i>
Ajeet K. Sharma, Johannes Venezian, Ayala Shiber, Günter Krämer, Bernd Bukau, Edward P. O’Brien
Abstract
Specifically, the 5' end cluster suppresses the formation of ribosome queues, reducing the interaction of ribosome-associated quality control factors with stalled ribosomes. We experimentally validate this prediction by introducing two nonoptimal clusters into three different genes and find that their mRNA half-life increases up to fourfold. The model also predicts that in the presence of two clusters, the cluster closest to the 5' end is the primary determinant of mRNA half-life. These results suggest the "translational ramp," in which nonoptimal codons are located near the start codon and increase translational efficiency, may have the additional biological benefit of allowing downstream slow-codon clusters to be present without decreasing mRNA half-life. These results indicate that codon usage bias plays a more nuanced role in controlling cellular protein levels than previously thought.