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Diabetes. 2017 Dec;66(12):2987-3000. doi: 10.2337/db17-0655. Epub 2017 Sep 29.

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

Author information

1
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China dxuwzmu@gmail.com.
2
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore.
3
School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore.
4
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
5
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA.
6
Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore.
7
Department of Endocrinology, Tan Tock Seng Hospital, Singapore.
8
Office of Clinical Sciences, Duke-NUS Medical School, Singapore.
9
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore sun.lei@duke-nus.edu.sg.
10
Institute of Molecular and Cell Biology, Singapore.

Abstract

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.

PMID:
28970281
DOI:
10.2337/db17-0655
[Indexed for MEDLINE]
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