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Publication : The CCR4-NOT Deadenylase Complex Maintains Adipocyte Identity.

First Author  Takahashi A Year  2019
Journal  Int J Mol Sci Volume  20
Issue  21 PubMed ID  31652943
Mgi Jnum  J:286151 Mgi Id  MGI:6400031
Doi  10.3390/ijms20215274 Citation  Takahashi A, et al. (2019) The CCR4-NOT Deadenylase Complex Maintains Adipocyte Identity. Int J Mol Sci 20(21):5274
abstractText  Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4-NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4-NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4-NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed.
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