Abstract
The CCR4-NOT complex is a highly conserved specific gene silencer that also serves more general post-transcriptional functions. Specific regulatory proteins including the miRNA-induced silencing complex and its associated proteins, bind to 3’-UTR elements of mRNA and recruit the CCR4-NOT complex thereby promoting poly(A) shortening and repressing translation and/or mRNA degradation. Recent studies have shown that the CCR4-NOT complex that is tethered to mRNA by such regulator(s) represses translation and facilitates mRNA decay independent of a poly(A) tail and its shortening. In addition to deadenylase activity, the CCR4-NOT complex also has an E3 ubiquitin ligase activity and is involved in a novel protein quality control system, i.e., co-translational proteasomal-degradation of aberrant proteins. In this review, we describe recent progress in elucidation of novel roles of the multi-functional complex CCR4-NOT in post-transcriptional regulation.
Highlights
CCR4-NOT is a highly conserved multiprotein complex that plays various roles in gene regulation
This review focuses on novel functional aspects of the CCR4-NOT complex in post-transcriptional regulation and provides insight into the mechanism of gene regulation by this conserved multi-functional complex and its associated regulators
In human and Drosophila melanogaster cells, gene silencing by miRNA involves GW182/TNRC6-mediated recruitment of CCR4-NOT through conserved W-containing motifs, Gly/Ser/Thr-Trp (G/S/TW) or Trp-Gly/Ser/Thr (WG/S/T), that are located in both the N-terminal and C-terminal effector domains of GW182/TNRC6 proteins (Chekulaeva et al, THE ROLE OF THE CCR4-NOT COMPLEX IN mRNA DECAPPING INDUCED BY miRNA mRNA degradation by miRNAs and GW182/TNRC6 requires both the CCR4-NOT deadenylase and the DCP1-DCP2 decapping complexes (Rehwinkel et al, 2005; Behm-Ansmant et al, 2006)
Summary
CCR4-NOT is a highly conserved multiprotein complex that plays various roles in gene regulation. The CCR4NOT complex is the main deadenylase and plays crucial roles in mRNA decay and translation repression induced by poly(A) shortening (Wahle and Winkler, 2013).
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