The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae

The major pathways of mRNA turnover in eukaryotes initiate with shortening of the poly(A) tail. We demonstrate by several criteria that CCR4 and CAF1 encode critical components of the major cytoplasmic deadenylase in yeast. F irst, both Ccr4p and Caf1p are required for normal mRNA deadenylation in vi vo. Second, both proteins localize to the cytoplasm. Third, purification of Caf1p copurifies with a Ccr4p-dependent poly(A)-specific exonuclease activ ity. We also provide evidence that the Pan2p/Pan3p nuclease complex encodes the predominant alternative deadenylase. These results, and previous work on Pan2p/Pan3p, define the mRNA deadenylases in yeast. The strong conservat ion of Ccr4p, Caf1p, Pan2p, and Pan3p indicates that they will function as deadenylases in other eukaryotes. Interestingly, because Ccr4p and Caf1p in teract with transcription factors, these results suggest an unexpected link between mRNA synthesis and turnover.