Figure 1 (A) General mRNA decay pathways. (B) Specialized mRNA decay pathways. R. Parker, unpublished data). However, it should be noted that 39 to 59 degradation of mRNAs is just slightly slower than decapping. For example, for the PGK1 and MFA2 mRNAs, computational analysis of experimental data has indicated that 39 to 59 decay is 1.5 and 6 times slower than decapping, respectively (Cao and Parker 2001). As assessed by a variety of different methods (Passos and Parker 2008; Munchel et al. 2011), the degradation rates of individual mRNAs can vary by over an order of magnitude. This was ﬁrst observed in decay rate measurements of groups of mRNAs (Herrick et al. 1990; Brown and Sachs 1998) and has now been conﬁrmed by multiple genome- wide studies of mRNA decay rates (Wang et al. 2002; Grigull et al. 2004; Munchel et al. 2011). The decay rates of mRNAs are somewhat clustered by the function of the encoded pro- tein (Herrick et al. 1990; Grigull et al. 2004; Wang et al. 2006; Beilharz and Preiss 2007). Differences in the decay rates of individual mRNAs can arise by differences in dead- enylation rates, decapping rates, or the rates of 39 to 59 deg- radation (Cao and Parker 2001; Beilharz and Preiss 2007). For example, the MFA2 mRNA (t1/2 = 39–49) differs from the relatively stable PGK1 mRNA (t1/2 = 309–459) by having faster rates of deadenylation (15 adenosines/min compared to 3 adenosines/min), decapping (0.0077 sec21 compared to 0.000462 sec21) and 39 to 59 degradation (0.0012 sec21 compared to 0.0003 sec21) (Cao and Parker 2001). Thus, to understand differential control of mRNA decay rates, one must consider the processes of deadenylation, decapping, and 39 to 59 degradation and how they are regulated. Deadenylation Two enzyme complexes catalyze poly(A) shortening (Table 1). The predominant deadenylase is the Ccr4/Pop2/Not complex (Daugeron et al. 2001; Tucker et al. 2001). This large complex consists of two active 39 to 59 exonucleases (Ccr4 and Pop2/Caf1) and includes the Not1, Not2, Not3, Not4, Not5, Caf40, and Caf130 proteins (Denis and Chen 2003). In yeast, at least during mid-log growth, the major deadenylase in this complex is the Ccr4 protein, a member of the ExoIII nuclease family, since mutations in the active site of this enzyme give defects in deadenylation similar to the ccr4Δ strain (Chen et al. 2002; Tucker et al. 2002). Ccr4 also interacts directly with the Pop2 protein through a leu- cine-rich-repeat region (Clark et al. 2004). RNA Decay in Yeast 673