Translational readthrough of the PDE2 stop codon modulates cAMP levels in Saccharomyces cerevisiae

Summary The efficiency of translation termination in yeast can vary several 100‐fold, depending on the context around the stop codon. We performed a computer analysis designed to identify yeast open reading frames (ORFs) containing a readthrough motif surrounding the termination codon. Eight ORFs were found to display inefficient stop codon recognition, one of which, PDE2 , encodes the high‐affinity cAMP phosphodiesterase. We demonstrate that Pde2p stability is very impaired by the readthrough‐dependent extension of the protein. A 20‐fold increase in readthrough of PDE2 was observed in a [ PSI + ] as compared with a [ psi – ] strain. Consistent with this observation, an important increase in cAMP concentration was observed in suppressor backgrounds. These results provide a molecular explanation for at least some of the secondary phenotypes associated with suppressor backgrounds.