TY - JOUR
T1 - RNA binding protein Ybx2 regulates RNA stability during cold-induced brown fat activation
AU - Xu, Dan
AU - Xu, Shaohai
AU - Kyaw, Aung Maung Maung
AU - Lim, Yen Ching
AU - Chia, Sook Yoong
AU - Siang, Diana Teh Chee
AU - Alvarez-Dominguez, Juan R.
AU - Chen, Peng
AU - Khee-Shing Leow, Melvin
AU - Sun, Lei
N1 - Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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 Pgc1a, that were destabilized by Ybx2 depletion during cold-induced activation. Thus, Ybx2 is a novel regulator that controls BAT activation by regulating mRNA stability.
AB - 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 Pgc1a, 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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U2 - 10.2337/db17-0655
DO - 10.2337/db17-0655
M3 - Article
C2 - 28970281
AN - SCOPUS:85035348056
SN - 0012-1797
VL - 66
SP - 2987
EP - 3000
JO - Diabetes
JF - Diabetes
IS - 12
ER -
