The RNA-binding protein HuR is a negative regulator in adipogenesis

Diana Teh Chee Siang, Yen Ching Lim, Aung Maung Maung Kyaw, Khaing Nwe Win, Sook Yoong Chia, Ufuk Degirmenci, Xiang Hu, Bryan C. Tan, Arcinas Camille Esther Walet, Lei Sun () and Dan Xu ()
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Diana Teh Chee Siang: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Yen Ching Lim: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Aung Maung Maung Kyaw: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Khaing Nwe Win: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Sook Yoong Chia: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Ufuk Degirmenci: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Xiang Hu: Departments of Endocrine and Metabolic Diseases, The first Affiliated Hospital of Wenzhou Medical University
Bryan C. Tan: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Arcinas Camille Esther Walet: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Lei Sun: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Dan Xu: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-14001-8

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