Identification and Characterization of Circular Intronic RNAs Derived from Insulin Gene.

Circular RNAs (circRNAs) are a large family of noncoding RNAs that have emerged as novel regulators of gene expression. However, little is known about the function of circRNAs in pancreatic β-cells. Here, transcriptomic analysis of mice pancreatic islet RNA-sequencing data identified 77 differentially expressed circRNAs between mice fed with a normal diet and a high-fat diet. Surprisingly, multiple circRNAs were derived from the intron 2 of the preproinsulin 2 () gene and are termed as circular intronic (). The expression of transcripts in mouse pancreatic islets, and βTC6 cells were confirmed by reverse transcription PCR, DNA sequencing, and RNase R treatment experiments. The level of was altered in βTC6 cells upon exposure to elevated levels of palmitate and glucose. Computational analysis predicted the interaction of several RNA-binding proteins with and their flanking region, suggesting their role in the function or biogenesis. Additionally, bioinformatics analysis predicted the association of several microRNAs with . Gene ontology and pathway analysis of genes targeted by miRNAs associated with suggested the regulation of several key biological processes. Together, our findings indicate that differential expression of circRNAs, especially transcripts, may regulate β-cell function and may play a critical role in the development of diabetes.