Post-transcriptional Stabilization of Ucp1 mRNA Protects Mice from Diet-Induced Obesity

Cell Reports

Miho Tokumasu¹  Tadashi Yamamoto¹  Toru Suzuki¹  Akinori Takahashi¹  Masahiro Morita²  Shungo Adachi³  Tohru Natsume³ 

[1] Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412, Japan;Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada;Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan;

关键词: deadenylation;    Cnot7;    Tob;    Ucp1;    obesity;   

DOI  :  10.1016/j.celrep.2015.11.056

来源: DOAJ

【 摘 要 】

Uncoupling protein 1 (Ucp1) contributes to thermogenesis, and its expression is regulated at the transcriptional level. Here, we show that Ucp1 expression is also regulated post-transcriptionally. In inguinal white adipose tissue (iWAT) of mice fed a high-fat diet (HFD), Ucp1 level decreases concomitantly with increases in Cnot7 and its interacting partner Tob. HFD-fed mice lacking Cnot7 and Tob express elevated levels of Ucp1 mRNA in iWAT and are resistant to diet-induced obesity. Ucp1 mRNA has an elongated poly(A) tail and persists in iWAT of Cnot7−/− and/or Tob−/− mice on a HFD. Ucp1 3′-UTR-containing mRNA is more stable in cells expressing mutant Tob that is unable to bind Cnot7 than in WT Tob-expressing cells. Tob interacts with BRF1, which binds to an AU-rich element in the Ucp1 3′-UTR. BRF1 knockdown partially restores the stability of Ucp1 3′-UTR-containing mRNA. Thus, the Cnot7-Tob-BRF1 axis inhibits Ucp1 expression and contributes to obesity.

【 授权许可】

Unknown