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Review
. 2021 Mar 1:24:212-222.
doi: 10.1016/j.omtn.2021.02.028. eCollection 2021 Jun 4.

Emerging roles of circular RNAs in systemic lupus erythematosus

Affiliations
Review

Emerging roles of circular RNAs in systemic lupus erythematosus

Xin Wang et al. Mol Ther Nucleic Acids. .

Abstract

Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures lacking 5'-3' polarity and a polyadenine tail. Over recent years, a growing body of studies have been conducted to explore the roles of circRNAs in human diseases. Systemic lupus erythematosus (SLE) is a severe autoimmune disorder characterized by the presence of autoantibodies and excessive inflammation, which impact multiple organs. Recent advances have begun to shed light on the roles of circRNAs in SLE, providing fresh insights into the pathogenesis of SLE and the latent capacity for translation into clinical applications. Here, we briefly introduce these "star molecules" and summarize their roles in SLE. In addition, we outline the limitations of the current studies and raise prospects for future research.

Keywords: circular RNA; expression; function; mechanism; systemic lupus erythematosus.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Generation, function, transmission, and degradation of circRNAs This process involves several important events. (A) The transcription of pre-mRNAs, which is modulated by epigenetic modifications and transcription factors. (B) The generation of circRNAs, which are a consequence of pre-mRNA back-splicing events such as lariat-driven circularization, intron pairing-driven circularization, and RBP-mediated circularization. (C) The biological functions of circRNAs, which are based on a variety of molecular regulatory mechanisms, including miRNA sponging, protein binding, transcription or splicing regulation, and peptide or protein coding. (D) The degradation of circRNAs, which is related to several molecular biological processes, such as Ago2-mediated RNA decay, m6A-driven circRNA degradation, and active RNase L triggered circRNA degradation. (E) The transmission of circRNAs from cells to body fluid, which endows them with the latent capacity to be biomarkers. (F) The transmission of circRNAs from body fluid to target cells, which is an important basis for mediating biological processes of target cells.
Figure 2
Figure 2
Prospective regulatory network of circRNAs in SLE There are several valuable and interesting points in the network. (A and B) The aberrant epigenetic modifications as well as anomalously expressed transcription factors and RBPs in SLE may be specific factors to explicate the dysregulation of circRNAs. (C) The binding between circRNAs and some nuclear RBPs may affect the production of antinuclear antibodies. (D) Co-operating with or modulating the epigenetic modifications of circRNAs in SLE may be responsible for the unusual level of some disease-related genes. (E) Acting as miRNA sponges is still the hottest topic on circRNAs currently. (F) Peptides or proteins encoded by circRNAs may either function in original cells or transmit to body fluid and target cells to exert roles.
Figure 3
Figure 3
Prospective transmission pathway of circRNAs in SLE circRNAs generated in blood cells may enter serum via exosomes or cell breakage. These circRNAs then enter other blood cells or transmit to tissue fluid and enter tissue cells, causing immune response, inflammation, and cell damage. Accordingly, circRNAs generated in tissue cells may also influence other tissue cells and blood cells.

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References

    1. Dörner T., Furie R. Novel paradigms in systemic lupus erythematosus. Lancet. 2019;393:2344–2358. - PubMed
    1. Durcan L., O’Dwyer T., Petri M. Management strategies and future directions for systemic lupus erythematosus in adults. Lancet. 2019;393:2332–2343. - PubMed
    1. Tsokos G.C. Autoimmunity and organ damage in systemic lupus erythematosus. Nat. Immunol. 2020;21:605–614. - PMC - PubMed
    1. Tsokos G.C., Lo M.S., Costa Reis P., Sullivan K.E. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat. Rev. Rheumatol. 2016;12:716–730. - PubMed
    1. Mohan C., Putterman C. Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat. Rev. Nephrol. 2015;11:329–341. - PubMed

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