PUF proteins control gene expression by binding to the 3'-untranslated regions 
of specific mRNAs and triggering mRNA decay or translational repression. Here we 
focus on the mechanism of PUF-mediated regulation. The yeast PUF protein, Mpt5p, 
regulates HO mRNA and stimulates removal of its poly(A) tail (i.e. 
deadenylation). Mpt5p repression in vivo is dependent on POP2, a component of 
the cytoplasmic Ccr4p-Pop2p-Not complex that deadenylates mRNAs. In this study, 
we elucidate the individual roles of the Ccr4p and Pop2p deadenylases in 
Mpt5p-regulated deadenylation. Both in vivo and in vitro, Pop2p and Ccr4p 
proteins are required for Mpt5p-regulated deadenylation of HO. However, the 
requirements for the two proteins differ dramatically: the enzymatic activity of 
Ccr4p is essential, whereas that of Pop2p is dispensable. We conclude that Pop2p 
is a bridge through which the PUF protein recruits the Ccr4p enzyme to the 
target mRNA, thereby stimulating deadenylation. Our data suggest that PUF 
proteins may enhance mRNA degradation and repress expression by both 
deadenylation-dependent and -independent mechanisms, using the same Pop2p bridge 
to recruit a multifunctional Pop2p complex to the mRNA.