Table 1 General factors involved in mRNA deadenylation Factor Ccr4/Pop2/Not complex Pan2/Pan3 complex Tpa1 Pab1 eRF3 (Sup35) Rpb4/Rpb7 Function Major mRNA deadenylase Ccr4 critical catalytic subunit, ExoIII family member Pop2: second catalytic subunit, RNaseD family member Not1: large scaffolding protein Not2–5, Caf130, Caf40: accessory proteins of unknown function Additional mRNA deadenylase Primarily functions in initial trimming of poly(A) tail Pan2: catalytic subunit; RNaseD family member Interacts with and stimulated by Pab1 Pan3: regulatory subunit Prolyl 4-hydroxylase Binds poly(A) Interacts with eRF1 and eRF3 Required for normal deadenylation and translation termination Major poly(A)-binding protein Inhibits Ccr4 deadenylase Stimulates Pan2/Pan3 complex May interact with eRF3 to affect deadenylation Couples deadenylation to decapping Subunit of translation termination complex Interacts with Pab1 and thereby may inﬂuence deadenylation rates Two subunits of RNA polymerase II Required for normal rates of deadenylation May exit from nucleus as part of mRNP to affect cytoplasmic deadenylation References Daugeron et al. (2001); Tucker et al. (2001, 2002); Chen et al. (2002) Brown et al. (1996); Boeck et al. (1996); Brown and Sachs (1998) Keeling et al. (2006); Henri et al. (2010); Kim et al. (2010) Caponigro and Parker (1995); Boeck et al. (1996); Cosson et al. (2002); Tucker et al. (2002); Hosada et al. (2003) Hosada et al. (2003); Funakoshi et al. (2007) Lotan et al. (2005, 2007) The Pop2/Caf1 protein, a member of the RNaseD family, is a second exonuclease in the Ccr4/Pop2/Not complex (Thore et al. 2003). Despite the presence of noncanonical residues in its active site, one report describes Pop2 puriﬁed from bacteria as having 39 exonuclease in vitro (Thore et al. 2003). However, all of the catalytic activity of Ccr4/Pop2 complexes puriﬁed from yeast is dependent on the Ccr4 active site, suggesting that Ccr4 is the critical active dead- enylase (Goldstrohm et al. 2007). Strains lacking Pop2/Caf1 show a defect in deadenylation, but this is due to Pop2 interacting with and promoting Ccr4 function since muta- tions in the active site of Pop2 do not alter deadenylation of reporter mRNAs and overexpression of Ccr4 suppresses the deadenylation defects seen in a pop2Δ strain (Tucker et al. 2002; Viswanathan et al. 2004). Since Pop2/Caf1 has cata- lytic activity and Pop2 orthologs in other organisms play catalytic roles in deadenylation (Goldstrohm and Wickens 2008), it remains a formal possibility that Pop2 may func- tion as a deadenylase under some conditions or for some mRNAs. The roles of the Not, Caf40, and Caf130 proteins in dead- enylation are not yet clear. One possibility is that they adapt the deadenylase complex to different mRNAs through the action of regulatory proteins. Consistent with this possibility, defects in some of the Not proteins can affect deadenylation of speciﬁc mRNAs (Tucker et al. 2002). An alternative is that the Not and Caf accessory proteins play roles in other func- tions of the Ccr4/Pop2/Not complex, which has been sug- 674 R. Parker gested to have roles in transcription initiation and elongation (Deluen et al. 2002; Swanson et al. 2003; Qiu et al. 2004; Kruk et al. 2011). A second deadenylase complex consists of the Pan2 and Pan3 proteins, with Pan2, a RNaseD family member, being the catalytic subunit (Boeck et al. 1996). Pan2 and Ccr4 appear to be the only major deadenylases since pan2Δ ccr4Δ strains are slow growing and show no deadenylation of reporter mRNAs (Tucker et al. 2001). The activity of Pan2 is promoted by Pab1 (Boeck et al. 1996), while Pab1 appears to inhibit the action of the Ccr4 complex (Tucker et al. 2002). This suggests that mRNAs with Pab1 bound to the poly(A) tail will be resistant to deadenylation by Ccr4/Pop2 but will be substrates for Pan2/Pan3. Thus, the speciﬁc deadenylase active on an mRNA will be inﬂuenced by the nature of the protein complex on its 39 poly(A) tail. The Pan2/Pan3 and Ccr4/Pop2/Not complexes appear to function in a temporal manner on most mRNAs with Pan2/ Pan3 ﬁrst acting to shorten the nascent poly(A) tail from 90 residues to 65, although this can vary a bit between different mRNAs (Brown and Sachs 1998). This step appears to happen quickly since the poly(A) tail lengths longer than 70 residues are typically not observed in yeast cells unless Pan2 is inactive (Brown and Sachs 1998). This implies that there is a difference between the accessibility of the 0–65 A residues of the poly(A) tail and the 39-most 25 nucleotides. Since Pab1 promotes Pan2 activity, one model is that this deadenylation reﬂects Pab1 bound to the ﬁrst 65