Circular RNAs in Kidney Disease and Cancer

Overview

Journal Nat Rev Nephrol

Specialty Nephrology

Date 2021 Aug 12

PMID 34381199

Citations 58

Authors

Anton Jan van Zonneveld

Malte Kolling

Roel Bijkerk

Johan M Lorenzen

Affiliations

Soon will be listed here.

Abstract

Circular RNAs (circRNAs) are a class of endogenously expressed regulatory RNAs with a single-stranded circular structure. They are generated by back splicing and their expression can be tightly regulated by RNA binding proteins. Cytoplasmic circRNAs can function as molecular sponges that inhibit microRNA-target interactions and protein function or as templates for the efficient generation of peptides via rolling circle amplification. They can also act as molecular scaffolds that enhance the reaction kinetics of enzyme-substrate interactions. In the nucleus, circRNAs might facilitate chromatin modifications and promote gene expression. CircRNAs are resistant to degradation and can be packaged in extracellular vesicles and transported in the circulation. Initial studies suggest that circRNAs have roles in kidney disease and associated cardiovascular complications. They have been implicated in hypertensive nephropathy, diabetic kidney disease, glomerular disease, acute kidney injury and kidney allograft rejection, as well as in microvascular and macrovascular complications of chronic kidney disease, including atherosclerotic vascular disease. In addition, several circRNAs have been reported to have oncogenic or tumour suppressor roles or to regulate drug resistance in kidney cancer. The available data suggest that circRNAs could be promising diagnostic and/or prognostic biomarkers and potential therapeutic targets for kidney disease, cardiovascular disease and kidney cancer.

Citing Articles

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Comprehensive analysis of differential mRNA and circRNA profiles in primary and metastatic pancreatic neuroendocrine tumors.

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Renal Tubular Epithelial Cell-Derived hsa_circ_0008925 From Urine Is Related to Chronic Renal Fibrosis.

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References

Salzman J, Gawad C, Wang P, Lacayo N, Brown P . Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012; 7(2):e30733. PMC: 3270023. DOI: 10.1371/journal.pone.0030733. View

Jeck W, Sorrentino J, Wang K, Slevin M, Burd C, Liu J . Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2012; 19(2):141-57. PMC: 3543092. DOI: 10.1261/rna.035667.112. View

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A . Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013; 495(7441):333-8. DOI: 10.1038/nature11928. View

Hansen T, Jensen T, Clausen B, Bramsen J, Finsen B, Damgaard C . Natural RNA circles function as efficient microRNA sponges. Nature. 2013; 495(7441):384-8. DOI: 10.1038/nature11993. View

Sanger H, KLOTZ G, Riesner D, Gross H, KLEINSCHMIDT A . Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A. 1976; 73(11):3852-6. PMC: 431239. DOI: 10.1073/pnas.73.11.3852. View

Berget S, Moore C, Sharp P . Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci U S A. 1977; 74(8):3171-5. PMC: 431482. DOI: 10.1073/pnas.74.8.3171. View

Nigro J, Cho K, Fearon E, Kern S, Ruppert J, Oliner J . Scrambled exons. Cell. 1991; 64(3):607-13. DOI: 10.1016/0092-8674(91)90244-s. View

Kos A, Dijkema R, Arnberg A, van der Meide P, Schellekens H . The hepatitis delta (delta) virus possesses a circular RNA. Nature. 1986; 323(6088):558-60. DOI: 10.1038/323558a0. View

Cocquerelle C, Mascrez B, Hetuin D, Bailleul B . Mis-splicing yields circular RNA molecules. FASEB J. 1993; 7(1):155-60. DOI: 10.1096/fasebj.7.1.7678559. View

10.

Bailleul B . During in vivo maturation of eukaryotic nuclear mRNA, splicing yields excised exon circles. Nucleic Acids Res. 1996; 24(6):1015-9. PMC: 145744. DOI: 10.1093/nar/24.6.1015. View

11.

Zhang X, Wang H, Zhang Y, Lu X, Chen L, Yang L . Complementary sequence-mediated exon circularization. Cell. 2014; 159(1):134-147. DOI: 10.1016/j.cell.2014.09.001. View

12.

Ashwal-Fluss R, Meyer M, Pamudurti N, Ivanov A, Bartok O, Hanan M . circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014; 56(1):55-66. DOI: 10.1016/j.molcel.2014.08.019. View

13.

Conn S, Pillman K, Toubia J, Conn V, Salmanidis M, Phillips C . The RNA binding protein quaking regulates formation of circRNAs. Cell. 2015; 160(6):1125-34. DOI: 10.1016/j.cell.2015.02.014. View

14.

Salzman J, Chen R, Olsen M, Wang P, Brown P . Cell-type specific features of circular RNA expression. PLoS Genet. 2013; 9(9):e1003777. PMC: 3764148. DOI: 10.1371/journal.pgen.1003777. View

15.

Delaleau M, Borden K . Multiple Export Mechanisms for mRNAs. Cells. 2015; 4(3):452-73. PMC: 4588045. DOI: 10.3390/cells4030452. View

16.

Huang C, Liang D, Tatomer D, Wilusz J . A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs. Genes Dev. 2018; 32(9-10):639-644. PMC: 6004072. DOI: 10.1101/gad.314856.118. View

17.

Hansen T, Wiklund E, Bramsen J, Villadsen S, Statham A, Clark S . miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J. 2011; 30(21):4414-22. PMC: 3230379. DOI: 10.1038/emboj.2011.359. View

18.

Park O, Ha H, Lee Y, Boo S, Kwon D, Song H . Endoribonucleolytic Cleavage of mA-Containing RNAs by RNase P/MRP Complex. Mol Cell. 2019; 74(3):494-507.e8. DOI: 10.1016/j.molcel.2019.02.034. View

19.

Lee Y, Choe J, Park O, Kim Y . Molecular Mechanisms Driving mRNA Degradation by mA Modification. Trends Genet. 2020; 36(3):177-188. DOI: 10.1016/j.tig.2019.12.007. View

20.

Liu C, Li X, Nan F, Jiang S, Gao X, Guo S . Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity. Cell. 2019; 177(4):865-880.e21. DOI: 10.1016/j.cell.2019.03.046. View