Identification and Characterization of Circular Intronic RNAs Derived from Insulin Gene

Int J Mol Sci. 2020 Jun 17;21(12):4302. doi: 10.3390/ijms21124302.


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 (Ins2) gene and are termed as circular intronic (ci)-Ins2. The expression of ci-Ins2 transcripts in mouse pancreatic islets, and βTC6 cells were confirmed by reverse transcription PCR, DNA sequencing, and RNase R treatment experiments. The level of ci-Ins2 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 ci-Ins2 and their flanking region, suggesting their role in the ci-Ins2 function or biogenesis. Additionally, bioinformatics analysis predicted the association of several microRNAs with ci-Ins2. Gene ontology and pathway analysis of genes targeted by miRNAs associated with ci-Ins2 suggested the regulation of several key biological processes. Together, our findings indicate that differential expression of circRNAs, especially ci-Ins2 transcripts, may regulate β-cell function and may play a critical role in the development of diabetes.

Keywords: diabetes; insulin splicing; lariat-derived circRNA; pancreatic β-cells; translation.

MeSH terms

  • Alternative Splicing
  • Base Sequence
  • Computational Biology / methods
  • Exons
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Insulin-Secreting Cells / metabolism
  • Insulins / genetics*
  • Introns
  • RNA Interference
  • RNA Splicing
  • RNA Splicing Factors / metabolism
  • RNA, Circular*
  • Transcriptome


  • Insulins
  • RNA Splicing Factors
  • RNA, Circular