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

被引：47

作者：

Takahashi, Akinori ^{[1
]}

Adachi, Shungo ^{[2
]}

Morita, Masahiro ^{[3
,4
]}

Tokumasu, Miho ^{[1
]}

Natsume, Tohru ^{[2
]}

Suzuki, Toru ^{[1
]}

Yamamoto, Tadashi ^{[1
]}

机构：

[1] Okinawa Inst Sci & Technol, Cell Signal Unit, Kunigami, Okinawa 9040412, Japan

[2] Natl Inst Adv Ind Sci & Technol, Mol Profiling Res Ctr Drug Discovery, Tokyo 1350064, Japan

[3] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada

[4] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada

来源：

CELL REPORTS | 2015年 / 13卷 / 12期

关键词：

UNCOUPLING PROTEIN-1 EXPRESSION; CCR4-NOT DEADENYLASE COMPLEX; ADAPTIVE THERMOGENESIS; STRUCTURAL BASIS; BROWN FAT; WHITE; GENE; TOB; DIFFERENTIATION; ADIPOCYTES;

D O I：

10.1016/j.celrep.2015.11.056

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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.

引用

页码：2756 / 2767

页数：12

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