Ccr4-Not complex: the control freak of eukaryotic cells

The purpose of this review is to provide an analysis of the latest developments on the functions of the carbon catabolite-repression 4-Not (Ccr4-Not) complex in regulating eukaryotic gene expression. Ccr4-Not is a nine-subunit protein complex that is conserved in sequence and function throughout the eukaryotic kingdom. Although Ccr4-Not has been studied since the 1980s, our understanding of what it does is constantly evolving. Once thought to solely regulate transcription, it is now clear that it has much broader roles in gene regulation, such as in mRNA decay and quality control, RNA export, translational repression and protein ubiquitylation. The mechanism of actions for each of its functions is still being debated. Some of the difficulty in drawing a clear picture is that it has been implicated in so many processes that regulate mRNAs and proteins in both the cytoplasm and the nucleus. We will describe what is known about the Ccr4-Not complex in yeast and other eukaryotes in an effort to synthesize a unified model for how this complex coordinates multiple steps in gene regulation and provide insights into what questions will be most exciting to answer in the future.