The CCR4–NOT Deadenylase Complex Maintains Adipocyte Identity

• Main Authors: Akinori Takahashi, Shohei Takaoka, Shungo Kobori, Tomokazu Yamaguchi, Sara Ferwati, Keiji Kuba, Tadashi Yamamoto, Toru Suzuki
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: International Journal of Molecular Sciences
• Subjects: ccr4–not complex; adipocyte; lipodystrophy
• Online Access: https://www.mdpi.com/1422-0067/20/21/5274

Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the <i>Cnot1</i> gene, which encodes an essential scaffold subunit of the CCR4&#8722;NOT deadenylase complex in adipose tissues (<i>Cnot1</i>-AKO mice) and we examined the role of CCR4&#8722;NOT in adipocyte function. <i>Cnot1</i>-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, <i>Cnot1</i>-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 <i>Cnot1</i>-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&#8722;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.