4cv5
From Proteopedia
yeast NOT1 CN9BD-CAF40 complex
Structural highlights
FunctionNOT1_YEAST Acts as component of the CCR4-NOT core complex, which in the nucleus seems to be a general transcription factor, and in the cytoplasm the major mRNA deadenylase involved in mRNA turnover. The NOT protein subcomplex negatively regulates the basal and activated transcription of many genes. Preferentially affects TC-type TATA element-dependent transcription. Could directly or indirectly inhibit component(s) of the general transcription machinery.[1] Publication Abstract from PubMedMicroRNAs (miRNAs) control gene expression by regulating mRNA translation and stability. The CCR4-NOT complex is a key effector of miRNA function acting downstream of GW182/TNRC6 proteins. We show that miRNA-mediated repression requires the central region of CNOT1, the scaffold protein of CCR4-NOT. A CNOT1 domain interacts with CNOT9, which in turn interacts with the silencing domain of TNRC6 in a tryptophan motif-dependent manner. These interactions are direct, as shown by the structure of a CNOT9-CNOT1 complex with bound tryptophan. Another domain of CNOT1 with an MIF4G fold recruits the DEAD-box ATPase DDX6, a known translational inhibitor. Structural and biochemical approaches revealed that CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity. Structure-based mutations showed that the CNOT1 MIF4G-DDX6 interaction is important for miRNA-mediated repression. These findings provide insights into the repressive steps downstream of the GW182/TNRC6 proteins and the role of the CCR4-NOT complex in posttranscriptional regulation in general. Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression.,Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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