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In eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5'cap structure and 3'poly(A) tail. These elements promote translation and prevent non-specific degradation. Degradation via the deadenylation-dependent 5'-3' degradation pathway can be induced by transacting factors binding the mRNA, such as RNA-binding proteins recognising sequence elements and the miRNA-induced repression complex. These factors recruit the core mRNA degradation machinery that carries out the following steps: i) shortening of the poly(A) tail by the Ccr4-Not and Pan2-Pan3 poly (A)-specific nucleases (deadenylases); ii) removal of the 5'cap structure by the Dcp1-Dcp2 decapping complex that is recruited by the Lsm1-7-Pat1 complex; and iii) degradation of the mRNA body by the 5'-3' exoribonuclease Xrn1. In this review, the biochemical function of the nucleases and accessory proteins involved in deadenylation-dependent mRNA degradation will be reviewed with a particular focus on structural aspects of the proteins and enzymes involved. [ABSTRACT FROM AUTHOR]

The CCR4-NOT complex is a highly conserved, multifunctional machinery with a general role in controlling mRNA metabolism. It has been implicated in a number of different aspects of mRNA and protein expression, including mRNA degradation, transcription initiation and elongation, ubiquitination, and protein modification. The core CCR4-NOT complex is evolutionarily conserved and consists of at least three NOT proteins and two catalytic subunits. The L-shaped complex is characterized by two functional modules bound to the CNOT1/Not1 scaffold protein: the deadenylase or nuclease module containing two enzymes required for deadenylation, and the NOT module. In this review, we will summarize the currently available information regarding the three-dimensional structure and assembly of the CCR4-NOT complex, in order to provide insight into its roles in mRNA degradation and other biological processes.

The shortening of the poly(A) tail of cytoplasmic mRNA (deadenylation) is a pivotal step in the regulation of gene expression in eukaryotic cells. Deadenylation impacts on both regulated mRNA decay as well as the rate of mRNA translation. An important enzyme complex involved in poly(A) shortening is the Ccr4-Not deadenylase. In addition to at least six non-catalytic subunits, it contains two distinct subunits with ribonuclease activity: a Caf1 subunit, characterised by a DEDD (Asp-Glu-Asp-Asp) domain, and a Ccr4 component containing an Endonuclease-Exonuclease-Phosphatase (EEP) domain. In vertebrate cells, the complexity of the complex is further increased by the presence of paralogues of the Caf1 subunit (encoded by either CNOT7 or CNOT8) and the occurrence of two Ccr4 paralogues (encoded by CNOT6 or CNOT6L). In plants, there are also multiple Caf1 and Ccr4 paralogues. Thus, the composition of the Ccr4-Not complex is heterogeneous. The potential differences in the intrinsic enzymatic activities of the paralogues will be discussed. In addition, the potential redundancy, cooperation and/or the extent of unique roles for the deadenylase subunits of the Ccr4-Not complex will be reviewed. Finally, novel approaches to study the catalytic roles of the Caf1 and Ccr4 subunits will be discussed.