RNA Binding Protein Ybx2 Regulates RNA Stability During Cold-Induced Brown Fat Activation

Diabetes - Tập 66 Số 12 - Trang 2987-3000 - 2017
Dan Xu1,2, Shaohai Xu3, Aung Maung Maung Kyaw1, Yen Ching Lim2, Sook Yoong Chia1, Diana Teh Chee Siang1, Juan R. Alvarez‐Dominguez4, Peng Chen3, Melvin Khee‐Shing Leow5,6,7, Lei Sun1,8
1Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore
2School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China
3School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore
4Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA
5Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore
6Department of Endocrinology, Tan Tock Seng Hospital, Singapore
7Office of Clinical Sciences, Duke-NUS Medical School, Singapore
8Institute of Molecular and Cell Biology, Singapore

Tóm tắt

Recent years have seen an upsurge of interest in brown adipose tissue (BAT) to combat the epidemic of obesity and diabetes. How its development and activation are regulated at the posttranscriptional level, however, has yet to be fully understood. RNA binding proteins (RBPs) lie in the center of posttranscriptional regulation. To systemically study the role of RBPs in BAT, we profiled >400 RBPs in different adipose depots and identified Y-box binding protein 2 (Ybx2) as a novel regulator in BAT activation. Knockdown of Ybx2 blocks brown adipogenesis, whereas its overexpression promotes BAT marker expression in brown and white adipocytes. Ybx2-knockout mice could form BAT but failed to express a full thermogenic program. Integrative analysis of RNA sequencing and RNA-immunoprecipitation study revealed a set of Ybx2’s mRNA targets, including Pgc1α, that were destabilized by Ybx2 depletion during cold-induced activation. Thus, Ybx2 is a novel regulator that controls BAT activation by regulating mRNA stability.

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