RNA-binding protein PTB and MicroRNA-221 coregulate AdipoR1 translation and adiponectin signaling

Yaniv Lustig, Ehud Barhod, Reut Ashwal-Fluss, Reut Gordin, Noam Shomron, Kfir Baruch-Umansky, Rina Hemi, Avraham Karasik, Hannah Kanety*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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 AdipoR1-39UTR 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.

Original languageEnglish
Pages (from-to)433-445
Number of pages13
JournalDiabetes
Volume63
Issue number2
DOIs
StatePublished - Feb 2014

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