Abstract
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, characterized 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 paralogs of the Caf1 subunit (encoded by either CNOT7 or CNOT8) and the occurrence of two Ccr4 paralogs (encoded by CNOT6 or CNOT6L). In plants, there are also multiple Caf1 and Ccr4 paralogs. Thus, the composition of the Ccr4-Not complex is heterogeneous. The potential differences in the intrinsic enzymatic activities of the paralogs 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.
Highlights
All mature protein-coding mRNAs in eukaryotic cells contain a 5 cap structure and a 3 poly(A) tail, with the notable exception of mRNAs encoding histones
The efficiency of initiation is enhanced by interactions between the cap and the poly(A) tail, which are mediated by the poly(A)-binding protein (PABP), the cap-binding factor eIF4E, and the intermediary scaffold eIF4G (Munroe and Jacobson, 1990; Gallie, 1991; Wells et al, 1998)
The Ccr4-Not nuclease module the Pan2-Pan3 complex can interact directly with the PABP, this interaction is indirect in case of the Ccr4-Not complex
Summary
All mature protein-coding mRNAs in eukaryotic cells contain a 5 cap structure and a 3 poly(A) tail, with the notable exception of mRNAs encoding histones. An important mechanism for the recruitment of both Ccr4-Not and the Pan2-Pan complex to specific mRNAs involves interactions with GW182/TNRC6 proteins, which are part of the miRNA repression complex (Chekulaeva et al, 2011; Fabian et al, 2011; Kuzuoglu-Ozturk et al, 2012; Huntzinger et al, 2013). In addition to these mechanisms of recruitment, the Pan2-Pan and Ccr4-Not deadenylases can bind to the poly(A)-binding protein (PABP).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call