Mutations in translation initiation factors lead to increased rates of deadenylation and decapping of mRNAs in Saccharomyces cerevisiae

The turnover of most mRNAs in Saccharomyces cerevisiae begins with deadenyl ation followed by decapping and 5'-->3' exonucleolytic digestion. An import ant question involves the mechanisms that allow particular mRNAs to exhibit different rates of both deadenylation and decapping. Since the cap structu re plays a critical role in the assembly of translation initiation factors, we hypothesized that the status of the cytoplasmic cap binding complex wou ld affect the rate of decapping. To test this hypothesis, we examined mRNA decay rates in yeast strains that were defective in several translation ini tiation factors that are part of the cap binding complex These experiments yielded three significant observations. First, any mutation known to inhibi t translation initiation also increased the rate of decapping. Second, deca pping still occurred only after deadenylation, suggesting that the ability of the poly(A) tail to inhibit decapping does not require efficient transla tion of the transcript. Third, mutants with defects in translation initiati on factors also showed an increase in the rate of deadenylation, suggesting that the rate of deadenylation may be controlled primarily by the translat ion status of the transcript. These results argue that the nature of the tr anslation initiation complex is a critical factor in determining the mRNA h alf-life. This view also implies that some cis-acting sequences that modula te mRNA decay rate do so by affecting the translation status of the transcr ipt.