CCR4Not

CCR4-NOT, also written CCR4-NOT complex, is a conserved multi-subunit complex that regulates gene expression at the post-transcriptional level. Its principal activity is mRNA deadenylation, the shortening of poly(A) tails, which commonly leads to decapping and mRNA decay. The complex also influences transcriptional regulation, mRNA export, and translation, and participates in RNA quality control and stress responses. It plays important roles in development and cellular differentiation and can affect the expression of specific transcripts and programs.

Structure: The complex centers on a scaffold subunit, NOT1 (CNOT1 in mammals), to which a modular set of regulatory subunits and two catalytic deadenylases are attached. The catalytic subunits include CCR4 (CNOT6/CNOT6L) and CAF1 (CNOT7/CNOT8). Additional regulatory subunits such as NOT2, NOT3, and NOT9 (CNOT9) contribute to complex assembly and substrate selection. The composition is conserved but varies among species.

Mechanism and recruitment: CCR4-NOT is recruited to target mRNAs by RNA-binding proteins and miRNA-induced silencing complexes. In miRNA pathways, GW182 proteins recruit CCR4-NOT to promote deadenylation and decay of targeted transcripts. The complex can also regulate translation and participate in cytoplasmic processing bodies.

Biological significance: Through controlled mRNA turnover, CCR4-NOT influences development, stem cell maintenance, and neuronal function. Misregulation of subunits has been linked to cancer and neurological disorders in some contexts.