When driving a car, control of the brakes is just as important as control of the accelerator pedal. Likewise, in gene expression, regulation of mRNA degradation is as important as regulation of its synthesis (Mühlemann, 2005). The rate-determining step of mRNA decay in eukaryotes seems to be the shortening of the poly(A) tail (deadenylation), as this step is slower than the subsequent decapping and degradation of the mRNA body. The Mega-Dalton Ccr4-Not complex contains two exonucleases, Ccr4p and Pop2p, responsible for this process. It is not known at present why two conserved nucleases are needed in the Ccr4-Not complex to degradation the poly(A) tail, if one is inactive in the complex or whether it is plausible that both are needed to account for different substrates. The structure of Pop2p from S. pombe was recently solved to very high resolution in our lab (Jonstrup et al., 2007). This structure reveals a detailed description of the conserved DEDD active site coordinating two magnesium ions important for the catalytic mechanism. We have investigated the physiological relevance of the ions in the active site of Pop2p both biochemically and structurally. Mühlemann , O.(2005. Nat Stru and Mol biol 12, 1024-1025. Jonstrup, A. T., Andersen, K. R., Van, L. B., and Brodersen, D. E. (2007). Nucl Acids Res, 35: 3153-3164.