RNA-Binding Protein PTB and MicroRNA-221 Coregulate AdipoR1 Translation and Adiponectin Signaling
- Yaniv Lustig1,
- Ehud Barhod1,2,
- Reut Ashwal-Fluss1,2,
- Reut Gordin1,2,
- Noam Shomron3,
- Kfir Baruch-Umansky4,
- Rina Hemi1,
- Avraham Karasik1,3 and
- Hannah Kanety1,3⇑
- 1Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Israel
- 2Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel
- 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- 4Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
- Corresponding author: Hannah Kanety, , or Yaniv Lustig, .
Adiponectin receptor 1 (AdipoR1) mediates adiponectin’s pleiotropic effects in muscle and liver and plays an important role in the regulation of insulin resistance and diabetes. Here, we demonstrate a pivotal role for microRNA-221 (miR-221) and the RNA-binding protein polypyrimidine tract–binding protein (PTB) in posttranscriptional regulation of AdipoR1 during muscle differentiation and in obesity. RNA-immunoprecipitation and luciferase reporter assays illustrated that both PTB and miR-221 bind AdipoR1-3′UTR and cooperatively inhibit AdipoR1 translation. Depletion of PTB or miR-221 increased, while overexpression of these factors decreased, AdipoR1 protein synthesis in both muscle and liver cells. During myogenesis, downregulation of PTB and miR-221 robustly induced AdipoR1 translation, providing a mechanism for enhanced AdipoR1 protein expression and activation in differentiated muscle cells. In addition, since both PTB and miR-221 are upregulated in liver and muscle of genetic and dietary mouse models of obesity, this novel translational mechanism may be at least partly responsible for the reduction in AdipoR1 protein levels in obesity. These findings highlight the importance of translational control in regulating AdipoR1 protein expression and adiponectin signaling. Given that adiponectin is reduced in obesity, induction of AdipoR1 could potentially enhance adiponectin beneficial effects and ameliorate insulin resistance and diabetes.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1032/-/DC1.
- Received July 1, 2013.
- Accepted October 10, 2013.
- © 2014 by the American Diabetes Association.
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