A Review on Circular RNA Translation and Its Implications in Disease

Overview

Journal Methods Mol Biol

Specialty Molecular Biology

Date 2024 Dec 20

PMID 39702706

Authors

Huanhuan Y Wei

Xiao-Juan Fan

Miao-Wei Mao

Affiliations

Soon will be listed here.

Abstract

The mRNA vaccine has emerged as a powerful tool against viral infection during the coronavirus disease 2019 (COVID-19) pandemic. In the post-COVID-19 era, the applications of mRNA-based therapy continue to expand and evolve. Circular RNA (circRNA), long assumed to be a noncoding RNA, has been proven to be translatable and subsequently developed as a next-generation mRNA modality due to its higher stability and wider therapeutic window. Nonetheless, the studies of circRNA translation and its application in diseases still present numerous technical features and challenges. In this chapter, we provide a summary and discussion on the mechanisms of circRNA translation and its applications in medicine development, aiming to serve as a reference and inspiration for readers interested in circRNA-based therapy.

References

Polack F, Thomas S, Kitchin N, Absalon J, Gurtman A, Lockhart S . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020; 383(27):2603-2615. PMC: 7745181. DOI: 10.1056/NEJMoa2034577. View

Baden L, El Sahly H, Essink B, Kotloff K, Frey S, Novak R . Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020; 384(5):403-416. PMC: 7787219. DOI: 10.1056/NEJMoa2035389. View

Wesselhoeft R, Kowalski P, Anderson D . Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat Commun. 2018; 9(1):2629. PMC: 6035260. DOI: 10.1038/s41467-018-05096-6. View

Wesselhoeft R, Kowalski P, Parker-Hale F, Huang Y, Bisaria N, Anderson D . RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo. Mol Cell. 2019; 74(3):508-520.e4. PMC: 6724735. DOI: 10.1016/j.molcel.2019.02.015. View

Qu L, Yi Z, Shen Y, Lin L, Chen F, Xu Y . Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell. 2022; 185(10):1728-1744.e16. PMC: 8971115. DOI: 10.1016/j.cell.2022.03.044. View

Liu X, Abraham J, Cheng Y, Wang Z, Wang Z, Zhang G . Synthetic Circular RNA Functions as a miR-21 Sponge to Suppress Gastric Carcinoma Cell Proliferation. Mol Ther Nucleic Acids. 2018; 13:312-321. PMC: 6197335. DOI: 10.1016/j.omtn.2018.09.010. View

Jost I, Shalamova L, Gerresheim G, Niepmann M, Bindereif A, Rossbach O . Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges. RNA Biol. 2018; 15(8):1032-1039. PMC: 6161685. DOI: 10.1080/15476286.2018.1435248. View

Lavenniah A, Luu T, Li Y, Lim T, Jiang J, Ackers-Johnson M . Engineered Circular RNA Sponges Act as miRNA Inhibitors to Attenuate Pressure Overload-Induced Cardiac Hypertrophy. Mol Ther. 2020; 28(6):1506-1517. PMC: 7264434. DOI: 10.1016/j.ymthe.2020.04.006. View

Schreiner S, Didio A, Hung L, Bindereif A . Design and application of circular RNAs with protein-sponge function. Nucleic Acids Res. 2020; 48(21):12326-12335. PMC: 7708053. DOI: 10.1093/nar/gkaa1085. View

10.

Bose R, Ain R . Regulation of Transcription by Circular RNAs. Adv Exp Med Biol. 2018; 1087:81-94. DOI: 10.1007/978-981-13-1426-1_7. View

11.

Li Z, Huang C, Bao C, Chen L, Lin M, Wang X . Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015; 22(3):256-64. DOI: 10.1038/nsmb.2959. View

12.

Vo J, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y . The Landscape of Circular RNA in Cancer. Cell. 2019; 176(4):869-881.e13. PMC: 6601354. DOI: 10.1016/j.cell.2018.12.021. View

13.

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

14.

Starke S, Jost I, Rossbach O, Schneider T, Schreiner S, Hung L . Exon circularization requires canonical splice signals. Cell Rep. 2014; 10(1):103-11. DOI: 10.1016/j.celrep.2014.12.002. View

15.

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

16.

Guo J, Agarwal V, Guo H, Bartel D . Expanded identification and characterization of mammalian circular RNAs. Genome Biol. 2014; 15(7):409. PMC: 4165365. DOI: 10.1186/s13059-014-0409-z. View

17.

Chen C, Sarnow P . Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science. 1995; 268(5209):415-7. DOI: 10.1126/science.7536344. View

18.

Wang Y, Wang Z . Efficient backsplicing produces translatable circular mRNAs. RNA. 2014; 21(2):172-9. PMC: 4338345. DOI: 10.1261/rna.048272.114. View

19.

Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y . Extensive translation of circular RNAs driven by N-methyladenosine. Cell Res. 2017; 27(5):626-641. PMC: 5520850. DOI: 10.1038/cr.2017.31. View

20.

Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O . Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017; 66(1):22-37.e9. PMC: 5387670. DOI: 10.1016/j.molcel.2017.02.017. View