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

Diana Teh Chee Siang,Arcinas Camille Esther Walet,Yen Ching Lim,Aung Maung Maung Kyaw,Xiang Hu,Bryan C Tan,Dan Xu,Sook Yoong Chia,Khaing Nwe Win,Lei Sun,Ufuk Degirmenci

doi:10.1038/s41467-019-14001-8

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.

Highlights

Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear
Our study establishes that HuR is an important posttranscriptional regulator of adipogenesis and provides insights into how posttranscriptional processes contribute to adipocyte development
These data are suggestive of a functional link between HuR and adipogenesis

Summary

Introduction

Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. Fat-specific knockout of HuR significantly enhances adipogenic gene program in adipose tissues, accompanied by a systemic glucose intolerance and insulin resistance. HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts including Insig[1], a negative regulator during adipogenesis. Our work establishes HuR as an important posttranscriptional regulator of adipogenesis and provides insights into how RNA processing contributes to adipocyte development. RNA-binding proteins (RBPs) play an essential role in governing the fate of mRNA transcripts from biogenesis, stabilization, translation to RNA decay[5,6]. Loss-of-HuR in adipose tissue significantly increase fat mass in mice, accompanied with glucose intolerance and insulin resistance. Our study establishes that HuR is an important posttranscriptional regulator of adipogenesis and provides insights into how posttranscriptional processes contribute to adipocyte development

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Conclusion