The CCR4-NOT complex plays diverse roles in mRNA metabolism

It is increasingly clear that the synthesis of eukaryotic mRNA involves an integrated series of events involving large multisubunit protein complexes. The evolutionarily conserved CCR4-NOT complex of proteins has been found to be involved in several aspects of mRNA formation, including repression and activation of mRNA initiation, control of mRNA elongation, and the deadenylation and subsequent degradation of mRNA. Its roles in such diverse processes make the CCR4-NOT complex central to the regulation of mRNA metabolism. In this review we describe the CCR4-NOT complex, its constituents, and its organization, discussing both the well characterized yeast proteins and their higher eukaryotic orthologs. The known biochemical roles of the individual components and of the complex are described with particular emphasis on the two known functions of the complex, repression of TFIID action and deadenylation of mRNA. Finally, the functional diversity of the CCR4-NOT complex is related to its mediating responses from a number of cellular signaling pathways.