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J. Biol. Chem., Vol. 281, Issue 44, 33386-33394, November 3, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/44/33386    most recent M604484200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gan, Z. Articles by Liu, Y. Search for Related Content PubMed PubMed Citation Articles by Gan, Z. Articles by Liu, Y. Social Bookmarking                      What's this?

RNA Editing by ADAR2 Is Metabolically Regulated in Pancreatic Islets and -Cells^*

From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China

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 -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 -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 -cell function.

Received for publication, May 10, 2006 , and in revised form, July 28, 2006.

^* This study was supported by the National Natural Science Foundation of China (Grants 30340059 and 30570391), Chinese Academy of Sciences (One Hundred Talents Program; Grant KSCX2-2-25), and Science and Technology Commission of Shanghai Municipality (Grants 03ZR14107 and 04DZ14007). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental table.

¹ To whom correspondence should be addressed. Tel.: 086-21-54920244; Fax: 086-21-54920291; E-mail: liuy{at}sibs.ac.cn.

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