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Review
. 2022 May 27;19(6):975-985.
doi: 10.7150/ijms.71840. eCollection 2022.

Advances in Circular RNA and Its Applications

Xian Zhao  1 , Youxiu Zhong  1 , Xudong Wang  1 , Jiuheng Shen  1 , Wenlin An  1
Affiliations
Review

Advances in Circular RNA and Its Applications

Xian Zhao et al. Int J Med Sci. .

Abstract

Circular RNA (circRNA) is a novel endogenous non-coding RNA (ncRNA) that, like microRNA (miRNA), is a rapidly emerging RNA research topic. CircRNA, unlike traditional linear RNAs (which have 5' and 3' ends), has a closed-loop structure that is unaffected by RNA exonucleases. Thus, circRNA has sustained expression and is less sensitive to degradation. Since circRNAs have many miRNAs binding sites, eliminating their repressive effects on their target genes can strongly enhance their expression. CircRNAs serve an important regulatory role in disease onset and progression via specific circRNA-miRNA interactions. We summarized the current progress in elucidating mechanisms and biogenesis of circRNAs in this review. In particular, circRNAs can function mainly as miRNA sponges, regulating host gene expression and protein transportation. Finally, we discussed the application prospects and significant challenges for the development of circRNA-based therapeutics.

Keywords: back-splicing; circRNA; circRNA-based therapeutics; mRNA; miRNA.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Fig 1
Fig 1
Biogenesis of circRNAs. A. The back-splicing circularization requires the help of the complementary sequences (ALU repeats and RCMs). B. RBP-mediated circularization. C. Lariat-driven circularization.
Fig 2
Fig 2
Biological functions of circRNAs. A. Acting as a miRNA sponge. B. In β-cells, ciRNA interacts with the RBP TDP-43 and controls the expression of genes necessary for insulin release. C. The circYap could bind with Yap mRNA, eIF4G and PABP simultaneously. Inhibiting this interaction represses the translation initiation of Yap. D. Regulation of nucleocytoplasmic transport. E. MDM2, an E3 ubiquitin-ligase, targets p53 for proteasome-dependent degradation. CircFoxo3 enhances the interaction between MDM2 and p53, and further promotes the poly-ubiquitination and degradation of p53. F. Translating to protein in a cap-independent manner.
See this image and copyright information in PMC

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