In eukaryotic organisms, initiation of mRNA turnover is controlled by 
progressive shortening of the poly-A tail, a process involving the mega-Dalton 
Ccr4-Not complex and its two associated 3'-5' exonucleases, Ccr4p and Pop2p 
(Caf1p). RNA degradation by the 3'-5' DEDDh exonuclease, Pop2p, is governed by 
the classical two metal ion mechanism traditionally assumed to be dependent on 
Mg(2+) ions bound in the active site. Here, we show biochemically and 
structurally that fission yeast (Schizosaccharomyces pombe) Pop2p prefers Mn(2+) 
and Zn(2+) over Mg(2+) at the concentrations of the ions found inside cells and 
that the identity of the ions in the active site affects the activity of the 
enzyme. Ion replacement experiments further suggest that mRNA deadenylation 
could be subtly regulated by local Zn(2+) levels in the cell. Finally, we use 
site-directed mutagenesis to propose a mechanistic model for the basis of the 
preference for poly-A sequences exhibited by the Pop2p-type deadenylases as well 
as their distributive enzymatic behavior.