The carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) complex serves as one of the major deadenylases of eukaryotes. Although it was originally identified and characterized in yeast, recent studies have revealed that the CCR4-NOT complex also exerts important functions in mammals, -including humans. However, there are some differences in the composition and functions of the CCR4-NOT complex between mammals and yeast. It is noteworthy that each subunit of the CCR4-NOT complex has unique, multifunctional roles and is responsible for various physiological phenomena. This heterogeneity and versatility of the CCR4-NOT complex makes an overall understanding of this complex difficult. Here, we describe the functions of each subunit of the mammalian CCR4-NOT complex and discuss the molecular mechanisms by which it regulates homeostasis in mammals. Furthermore, a possible link between the disruption of the CCR4-NOT complex and various diseases will be discussed. Finally, we propose that the analysis of mice with each CCR4-NOT subunit knocked out is an effective strategy for clarifying its complicated functions and networks in mammals.
Keywords: CCR4-NOT; deadenylation; knockout mice; mRNA decay; posttranscriptional regulation.