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Review
. 2014 Aug 21:5:286.
doi: 10.3389/fgene.2014.00286. eCollection 2014.

Multifunctional roles of the mammalian CCR4-NOT complex in physiological phenomena

Yo-Taro Shirai  1 , Toru Suzuki  1 , Masahiro Morita  2 , Akinori Takahashi  1 , Tadashi Yamamoto  1
Affiliations
Review

Multifunctional roles of the mammalian CCR4-NOT complex in physiological phenomena

Yo-Taro Shirai et al. Front Genet. .

Abstract

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.

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Figures

FIGURE 1
FIGURE 1
The mammalian carbon catabolite repression 4 (CCR4)–negative on TATA-less (NOT) complex exerts deadenylase activities guided by RNA-binding proteins, miRISC and Tob. (A) Schematic structural organization of the mammalian CCR4–NOT complex. It comprises either of CNOT6/6L and either of CNOT7/8 as deadenylase subunits. (B) Schematic representation of deadenylation by the mammalian CCR4–NOT complex. The CCR4–NOT complex is recruited to the 3′UTR of specific mRNAs through an interaction with AU-rich RNA binding proteins (AUBP) including TTP. GW182 is a component of miRISC together with miRNA and AGO. The CCR4–NOT complex is involved in the miRNA-induced deadenylation through an association with GW182. Tob also interacts with poly(A)-binding protein (PABP) and polyadenylation element-binding protein (CPEB), and recruits the CCR4–NOT complex to initiate deadenylation.
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