Xu, D., Xu, S., Kyaw, A. M. M., Lim, Y. C., Chia, S. Y., Chee Siang, D. T., … Sun, L. (2017). RNA Binding Protein Ybx2 Regulates RNA Stability During Cold-Induced Brown Fat Activation. Diabetes, 66(12), 2987–3000. doi:10.2337/db17-0655
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.
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Funding Info:
This work was supported by Singapore National Research Foundation (NRF) fellowship (NRFF) (NRF-2011NRF-NRFF 001-025) to L.S. This research is also supported by the Singapore NRF under its Cooperative Basic Research Grant (CBRG) grant administrated by the Singapore Ministry of Health's National Medical Research Council (NMRC) (NMRC/CBRG/0070/2014 and NMRC/CBRG/0101/2016).The project was funded by
Singapore National Research Foundation (NRF) fellowship (NRFF) (NRF-2011NRF-NRFF 001-025) to L.S. This research is also supported by the Singapore NRF under its Cooperative Basic Research Grant (CBRG) grant administrated by the Singapore Ministry of Health's National Medical Research Council (NMRC) (NMRC/CBRG/0070/2014 and NMRC/CBRG/0101/2016)