The RNA-binding protein HuR is a negative regulator in adipogenesis
The RNA-binding protein HuR is a negative regulator in adipogenesis
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DOI：
10.1038/s41467-019-14001-8
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发表时间：
2020-01-10
影响因子：
16.6
通讯作者：
Xu, Dan
中科院分区：
文献类型：
--
作者：
Siang, Diana Teh Chee;Lim, Yen Ching;Xu, Dan
人类抗原R（HuR）是RNA代谢的重要调节因子，但其在代谢中的功能仍不清楚。这项研究确定 HuR 是脂肪形成过程中的主要抑制因子。原代脂肪细胞培养物中 HuR 的敲低和过表达分别增强和抑制体外脂肪生成。脂肪特异性敲除 HuR 显着增强脂肪组织中的脂肪形成基因程序，并伴有系统性葡萄糖不耐受和胰岛素抵抗。 HuR 敲除还会导致库特异性表型：它可以抑制棕色脂肪中的肌生成程序，增强附睾白色脂肪中的炎症程序并诱导腹股沟白色脂肪中的褐变程序。从机制上讲，HuR 可能通过识别和调节数百种脂肪细胞转录物的稳定性来抑制脂肪生成，其中包括 Insig1（脂肪生成过程中的负调节因子）。总而言之，我们的工作将 HuR 确立为脂肪生成的重要转录后调节因子，并提供了有关 RNA 加工如何促进脂肪细胞发育的见解。
Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively. Fat-specific knockout of HuR significantly enhances adipogenic gene program in adipose tissues, accompanied by a systemic glucose intolerance and insulin resistance. HuR knockout also results in depot-specific phenotypes: it can repress myogenesis program in brown fat, enhance inflammation program in epidydimal white fat and induce browning program in inguinal white fat. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts including Insig1, a negative regulator during adipogenesis. Taken together, our work establishes HuR as an important posttranscriptional regulator of adipogenesis and provides insights into how RNA processing contributes to adipocyte development.