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RNA circularization strategies in vivo and in vitro
Open accessAbstract
In the plenitude of naturally occurring RNAs, circular RNAs (circRNAs) and their biological role were underestimated for years. However, circRNAs are ubiquitous in all domains of life, including eukaryotes, archaea, bacteria and viruses, where they can fulfill diverse biological functions. Some of those functions, as for example playing a role in the life cycle of viral and viroid genomes or in the maturation of tRNA genes, have been elucidated; other putative functions still remain elusive. Due to the resistance to exonucleases, circRNAs are promising tools for in vivo application as aptamers, trans-cleaving ribozymes or siRNAs. How are circRNAs generated in vivo and what approaches do exist to produce ring-shaped RNAs in vitro? In this review we illustrate the occurrence and mechanisms of RNA circularization in vivo, survey methods for the generation of circRNA in vitro and provide appropriate protocols.
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“A ribozymatic method utilizing a permuted group I catalytic intron has been reported to be more applicable to long RNA circularization and requires only the addition of GTP and Mg2+ as cofactors17.”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [17]
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“In vitro, these constructs undergo the double transesterification reactions characteristic of group I catalytic introns, but because the exons are already fused they are excised as covalently 5′ to 3′ linked circles17 (Fig. 1a).”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [17]
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Nichols, N. M., Tabor, S., & McReynolds, L. A. (2008) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb0315s84 · Cited by 16
Preparation of modified long-mer RNAs and analysis of FMN binding to theypaAaptamer fromB. subtilis
Frommer, J., Hieronymus, R., Arunachalam, T. S., Heeren, S., Jenckel, M., Strahl, A., Appel, B., & Müller, S. (2014) · RNA Biology · doi:10.4161/rna.28526 · Cited by 15
Self-citationSynthesis of Infectious Viroids and Other Circular RNAs
Rezaian, M. A. (1999) · Current Issues in Molecular Biology · doi:10.21775/cimb.001.013 · Cited by 14
A general two-step strategy to synthesize lariat RNAs
Wang, Y., & Silverman, S. K. (2005) · RNA · doi:10.1261/rna.2259406 · Cited by 14
Production of circular form of streptavidin RNA aptamer in vitro
Umekage, S., & Kikuchi, Y. (2006) · Nucleic Acids Symposium Series · doi:10.1093/nass/nrl161 · Cited by 13
Hairpin ribozyme-antisense RNA constructs can act as molecular lassos
Dallas, A., Balatskaya, S. V., Kuo, T.-C., Ilves, H., Vlassov, A. V., Kaspar, R. L., Kisich, K. O., Kazakov, S. A., & Johnston, B. H. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn637 · Cited by 13
Production of circular streptavidin RNA aptamer in vivo
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Ochi, A., Umekage, S., & Kikuchi, Y. (2009) · Nucleic Acids Symposium Series · doi:10.1093/nass/nrp138 · Cited by 8
Synthesis of Dumbbell‐Shaped Cyclic RNAs for RNA Interference
Abe, N., Abe, H., & Ito, Y. (2012) · Current Protocols in Nucleic Acid Chemistry · doi:10.1002/0471142700.nc1604s48 · Cited by 7
Synthetic nanocircular RNA for controlling of gene expression
Abe, H., Abe, N., Uda, M., Tsuneda, S., & Ito, Y. (2009) · Nucleic Acids Symposium Series · doi:10.1093/nass/nrp033 · Cited by 5
Turunen, J. J., Pavlova, L. V., Hengesbach, M., Helm, M., Müller, S., Hartmann, R. K., & Frilander, M. J. (2014) · doi:10.1002/9783527647064.ch3 · Cited by 5
Self-citationCircular RNA interference effector molecules (WO10084371)
Lundin, P., Moreno, P. M. D., Smith, C. E., & Andaloussi, S. E. (2010) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2011.534460 · Cited by 4
Nanocircular RNAs for RNA interference
Abe, H., Abe, N., Harada, M., Tsuneda, S., & Ito, Y. (2008) · Nucleic Acids Symposium Series · doi:10.1093/nass/nrn256 · Cited by 3
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Circular RNA: a new star of noncoding RNAs
Qu, S., Yang, X., Li, X., Wang, J., Gao, Y., Shang, R., Sun, W., Dou, K., & Li, H. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.06.003 · Cited by 1,808
Engineering circular RNA for potent and stable translation in eukaryotic cells
Wesselhoeft, R. A., Kowalski, P. S., & Anderson, D. G. (2018) · Nature Communications · doi:10.1038/s41467-018-05096-6 · Cited by 853
Translation and functional roles of circular RNAs in human cancer
Lei, M., Zheng, G., Ning, Q., Zheng, J., & Dong, D. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1135-7 · Cited by 814
Detecting circular RNAs: bioinformatic and experimental challenges
Szabo, L. A., & Salzman, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.114 · Cited by 684
CircHIPK3 sponges miR‐558 to suppress heparanase expression in bladder cancer cells
Li, Y., Zheng, F., Xiao, X., Xie, F., Tao, D., Huang, C., Liu, D., Wang, M., Wang, L., Zeng, F., et al. (2017) · EMBO Reports · doi:10.15252/embr.201643581 · Cited by 562
Metadata
- Authors
- Petkovic, S., & Müller, S.
- Affiliations
- Universität Greifswald (DE)
- Corresponding author
- Müller, Sabine
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-02-06
- Volume
- 43
- Issue
- 4
- Pages
- 2454-2465
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4344496
- OpenAlex
- W2121626677
- Cited by
- 386
- References
- 128
- Citations by year
- 2026: 21 · 2025: 42 · 2024: 51 · 2023: 39 · 2022: 40 · 2021: 51 · 2020: 46 · 2019: 31 · 2018: 26 · 2017: 18 · 2016: 15 · 2015: 5
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Oxford
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- circular RNA, RNA circularization, aptamers, siRNA, tRNA maturation, RNA biogenesis
- MeSH terms
- RNA, Circular, Exons, Introns, RNA Ligase (ATP), RNA, RNA, Viral, RNA, Archaeal
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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