The CCR4-NOT deadenylase complex regulates obesity via mRNA decay

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860761
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: TAKAHASHI Akinori 沖縄科学技術大学院大学, その他の研究科, 研究員 (90637589)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: Obesity / The CCR4-NOT complex / mRNA decay

Outline of Final Research Achievements

Obesity is a risk factor of various lifestyle diseases. Understanding of detail molecular mechanisms underlying obesity is required for invention of novel therapeutic approaches. The CCR4-NOT complex is a major eukaryotic deadenylase, and CNOT8 is one of the enzymatic subunits. The CCR4-NOT complex is implicated in obesity. To investigate molecular mechanism, we used liver-specific CNOT8 knockout mice model. We found that CNOT8 negatively regulates Egfr expression and contributes to obesity. Interestingly, CNOT8 regulates Egfr mRNA via deadenylation-independent post-transcriptional mechanism. Our study will provide a novel molecular mechanism of obesity and a new in vivo model of deadenylation-independent prost-transcriptional regulation.

Free Research Field

Molecular biology