RNA editing by ADAR2 is metabolically regulated in pancreatic islets and beta-cells.
RNA editing via the conversion of adenosine (A) to inosine (I) is catalyzed by two major families of adenosine deaminases acting on RNA (ADARs), ADAR1 and ADAR2. This genetic recoding process is known to play essential roles in the brain, due in part to changes in functional activities of edited neurotransmitter receptors and ion channels. Little is known, however, about the physiological regulation and function of A to I RNA editing in peripheral tissues and other biological processes. Here, we report that both ADAR1 and ADAR2 are expressed in the murine pancreatic islets, and ADAR2 is primarily localized in the islet endocrine cells. In contrast to ADAR1, ADAR2 transcripts in the pancreatic islets exhibit a nearly 2-fold increase in insulin-resistant mice chronically fed a high fat diet. Concurrent with this diet-induced metabolic stress, RNA editing in the islets is dramatically enhanced for the RNA transcripts encoding the ionotropic glutamate receptor subunit B. Moreover, ADAR2 protein expression is repressed in the islets under fuel deficiency condition during fasting, and this repression can be completely reversed by refeeding. We also show that, specifically in pancreatic beta-cell lines, not only the expression of ADAR2 but also the glutamate receptor subunit B editing and ADAR2 self-editing are markedly augmented in response to glucose at the physiological concentration for insulin secretion stimulation. Thus, RNA editing by ADAR2 in pancreatic islets and beta-cells is metabolically regulated by nutritional and energy status, suggesting that A to I RNA editing is most likely involved in the modulation of pancreatic islet and beta-cell function.
Gan
Zhenji
Z
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhao
Liyun
L
Yang
Liu
L
Huang
Ping
P
Zhao
Feng
F
Li
Wenjun
W
Liu
Yong
Y
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D002460:Cell Line; D005223:Fats / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism; D017393:RNA Editing / Q000235:genetics*; D016601:RNA-Binding Proteins; D051381:Rats; D017470:Receptors, Glutamate / Q000235:genetics; D015854:Up-Regulation
D005223:Fats; D016601:RNA-Binding Proteins; D017470:Receptors, Glutamate; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D005947:Glucose