c-jun amino-terminal kinase-1 mediates glucose-responsive upregulation of the rna editing enzyme adar2 in pancreatic beta-cellsc-jun伴激酶1介导glucose-responsive upregulation rna编辑酶adar2胰岛细胞.pdfVIP

c-Jun Amino-Terminal Kinase-1 Mediates Glucose- Responsive Upregulation of the RNA Editing Enzyme ADAR2 in Pancreatic Beta-Cells 1. 1. 1 1 1 1 1¤ Liu Yang , Ping Huang , Feng Li , Liyun Zhao , Yongliang Zhang , Shoufeng Li , Zhenji Gan , 2 1 1 Anning Lin , Wenjun Li , Yong Liu * 1 Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China, 2 State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Abstract A-to-I RNA editing catalyzed by the two main members of the adenosine deaminase acting on RNA (ADAR) family, ADAR1 and ADAR2, represents a RNA-based recoding mechanism implicated in a variety of cellular processes. Previously we have demonstrated that the expression of ADAR2 in pancreatic islet b-cells is responsive to the metabolic cues and ADAR2 deficiency affects regulated cellular exocytosis. To investigate the molecular mechanism by which ADAR2 is metabolically regulated, we found that in cultured b-cells and primary islets, the stress-activated protein kinase JNK1 mediates the upregulation of ADAR2 in response to changes of the nutritional state. In parallel with glucose induction of ADAR2 expression, JNK phosphorylation was concurrently increased in insulin-secreting INS-1 b-cells. Pharmacological inhibition of JNKs or siRNA knockdown of the expression of JNK1 prominently suppressed glucose-augmented ADAR2 expression, resulting in decreased efficiency