The yeast POP2 gene encodes a nuclease involved in mRNA deadenylation

The major mRNA degradation pathway involves deadenylation of the target mol ecule followed by decapping and, finally, 5'-->3' exonuclease digestion of the mRNA body. While yeast factors involved in the decapping and exonucleas e degradation steps have been identified, the nature of the factor(s) invol ved in the deadenylation step remained elusive. Database searches for yeast proteins related to the mammalian deadenylase PARN identified the Pop2 pro tein (Pop2p) as a potential deadenylase. While Pop2p was previously identif ied as a factor affecting transcription, we identified a non-canonical RNas e D sequence signature in its sequence. Analysis of the fate of a reporter mRNA in a pop2 mutant demonstrates that Pop2p is required for efficient mRN A degradation in vivo. Characterisation of mRNA degradation intermediates a ccumulating in this mutant supports the involvement of Pop2p in mRNA deaden ylation in vivo. Similar phenotypes are observed in yeast strains lacking t he Ccr4 protein, which is known to be associated with Pop2p, A recombinant Pop2p fragment encompassing the putative catalytic domain degrades poly(A) in vitro demonstrating that Pop2p is a nuclease, We also demonstrate that p oly(A) is a better competitor than poly(G) or poly(C) of the Pop2p nuclease activity. Altogether, our study indicates that Pop2p is a nuclease subunit of the yeast deadenylase and suggests that Pop2p homologues in other speci es may have similar functions.