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Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation – published online 01/02/2020

Zhang figure

Fang Fang Zhang, Yu Hong Liu, Dan Wei Wang, Ting Sheng Liu, Yue Yang, Jia Min Guo, Yi Pan, Yan Feng Zhang, Hong Du, Ling Li, Liang Jin

Abnormal expression of long non-coding RNAs (lncRNAs) has been associated with a variety of human diseases, including diabetes. However, it is unclear whether islet lncRNAs are involved in obesity-mediated beta cell dysfunction, which is associated with diabetes. In this issue, Zhang et al ( report that obesity reduces the expression of the lncRNA 1810019D21Rik (referred to as regulator of insulin transcription [ROIT]), as assessed by RNA sequencing analysis. They also show that over-expression of ROIT lncRNA leads to improved glucose homeostasis and insulin transcription. The authors suggest that this may be because ROIT lncRNA can downregulate the methylation of the Nkx6.1 promoter by binding to DNA methyltransferase 3a and causing its degradation. The authors conclude that these findings indicate that at least some of the harmful effects of obesity on beta cell function may be mediated by obesity-induced alterations in the level of the ROIT lncRNA.

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