RNA decay machines: Deadenylation by the Ccr4–Not and Pan2–Pan3 complexes

Shortening and removal of the 3′ poly(A) tail of mature mRNA by poly(A)-specific 3′ exonucleases (deadenylases) is the initial and often rate-limiting step in mRNA degradation. The majority of cytoplasmic deadenylase activity is associated with the Ccr4–Not and Pan2–Pan3 complexes. Two distinct catalytic subunits, Caf1/Pop2 and Ccr4, are associated with the Ccr4–Not complex, whereas the Pan2 enzymatic subunit forms a stable complex with Pan3. In this review, we discuss the composition and activity of these two deadenylases. In addition, we comment on generic and specific mechanisms of recruitment of Ccr4–Not and Pan2–Pan3 to mRNAs. Finally, we discuss specialised and redundant functions of the deadenylases and review the importance of Ccr4–Not subunits in the regulation of physiological processes. This article is part of a Special Issue entitled: RNA Decay mechanisms. ► Structures and catalytic mechanisms of the Ccr4–Not and PAN deadenylases are being elucidated. ► Deadenylase subunits and complexes play specialised as well as redundant roles. ► Deadenylase complexes can be recruited to mRNAs by protein- or RNA-dependent mechanisms. ► Knock-out mice reveal specific roles of individual Ccr4–Not subunits in biological processes.