Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 2,702

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Detecting and characterizing circular RNAs

Open access
Jeck, William R, Sharpless, Norman E·2014·Nature Biotechnology

Abstract

Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed comprehensive studies of circular RNA species. Recent studies have revealed thousands of endogenous circular RNAs in mammalian cells, some of which are highly abundant and evolutionarily conserved. Evidence is emerging that some circRNAs might regulate microRNA (miRNA) function, and roles in transcriptional control have also been suggested. Therefore, study of this class of noncoding RNAs has potential implications for therapeutic and research applications. We believe the key future challenge for the field will be to understand the regulation and function of these unusual molecules.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nbt.2890

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 8 references

Research works printed but not linked: 45

  1. Nigro, J.M. et al. Scrambled exons. Cell 64, 607–613 (1991). · DOI · Paper page
  2. Cocquerelle, C., Mascrez, B., Hétuin, D. & Bailleul, B. Mis-splicing yields circular RNA molecules. FASEB J 7, 155–160 (1993). · DOI · Paper page
  3. Kos, A., Dijkema, R., Arnberg, A.C., van der Meide, P.H. & Schellekens, H. The hepatitis delta (delta) virus possesses a circular RNA. Nature 323, 558–560 (1986). · DOI · Paper page
  4. Arnberg, A.C., van Ommen, G.J., Grivell, L.A., Van Bruggen, E.F. & Borst, P. Some yeast mitochondrial RNAs are circular. Cell 19, 313–319 (1980). · DOI · Paper page
  5. van der Veen, R. et al. Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro. Cell 44, 225–234 (1986). · DOI · Paper page
  6. Cocquerelle, C., Daubersies, P., Majérus, M.A., Kerckaert, J.P. & Bailleul, B. Splicing with inverted order of exons occurs proximal to large introns. EMBO J. 11, 1095–1098 (1992). · DOI · Paper page
  7. Capel, B. et al. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 73, 1019–1030 (1993). · DOI · Paper page
  8. Zaphiropoulos, P.G. Differential expression of cytochrome P450 2C24 transcripts in rat kidney and prostate: evidence indicative of alternative and possibly trans splicing events. Biochem. Biophys. Res. Commun. 192, 778–786 (1993). · doi:10.1006/bbrc.1993.1482
  9. Zaphiropoulos, P.G. Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping. Proc. Natl. Acad. Sci. USA 93, 6536–6541 (1996). · DOI · Paper page
  10. Caudevilla, C. et al. Natural trans-splicing in carnitine octanoyltransferase pre-mRNAs in rat liver. Proc. Natl. Acad. Sci. USA 95, 12185–12190 (1998). · doi:10.1073/pnas.95.21.12185
  11. Frantz, S.A. et al. Exon repetition in mRNA. Proc. Natl. Acad. Sci. USA 96, 5400–5405 (1999). · doi:10.1073/pnas.96.10.5400
  12. Surono, A. Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing. Hum. Mol. Genet. 8, 493–500 (1999). · DOI
  13. Rigatti, R. Exon repetition: a major pathway for processing mRNA of some genes is allele-specific. Nucleic Acids Res. 32, 441–446 (2004). · DOI
  14. Cocquet, J., Chong, A., Zhang, G. & Veitia, R.A. Reverse transcriptase template switching and false alternative transcripts. Genomics 88, 127–131 (2006). · DOI · Paper page
  15. McManus, C.J., Duff, M.O., Eipper-Mains, J. & Graveley, B.R. Global analysis of trans-splicing in Drosophila. Proc. Natl. Acad. Sci. USA 107, 12975–12979 (2010). · DOI
  16. Tabak, H.F. et al. Discrimination between RNA circles, interlocked RNA circles and lariats using two-dimensional polyacrylamide gel electrophoresis. Nucleic Acids Res. 16, 6597–6605 (1988). · DOI
  17. Hurowitz, E.H. & Brown, P.O. Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae. Genome Biol. 5, R2 (2003). · DOI
  18. Schindler, C.W., Krolewski, J.J. & Rush, M.G. Selective trapping of circular double-stranded DNA molecules in solidifying agarose. Plasmid 7, 263–270 (1982). · doi:10.1016/0147-619x(82)90007-5
  19. Hansen, T.B. et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J. 30, 4414–4422 (2011). · DOI · Paper page
  20. Suzuki, H. et al. Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res. 34, e63 (2006). · DOI · Paper page
  21. Salzman, J., Gawad, C., Wang, P.L., Lacayo, N. & Brown, P.O. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS ONE 7, e30733 (2012). · DOI · Paper page
  22. Gao, K., Masuda, A., Matsuura, T. & Ohno, K. Human branch point consensus sequence is yUnAy. Nucleic Acids Res. 36, 2257–2267 (2008). · DOI · Paper page
  23. Salzman, J., Chen, R.E., Olsen, M.N., Wang, P.L. & Brown, P.O. Cell-type specific features of circular RNA expression. PLoS Genet. 9, e1003777 (2013). · DOI · Paper page
  24. Fonseca, N.A., Rung, J., Brazma, A. & Marioni, J.C. Tools for mapping high-throughput sequencing data. Bioinformatics 28, 3169–3177 (2012). · DOI · Paper page
  25. Danan, M., Schwartz, S., Edelheit, S. & Sorek, R. Transcriptome-wide discovery of circular RNAs in Archaea. Nucleic Acids Res. 40, 3131–3142 (2012). · DOI · Paper page
  26. Brown, J.A., Valenstein, M.L., Yario, T.A., Tycowski, K.T. & Steitz, J.A. Formation of triple-helical structures by the 3′-end sequences of MALAT1 and MENβ noncoding RNAs. Proc. Natl. Acad. Sci. USA 109, 19202–19207 (2012). · DOI · Paper page
  27. Wilusz, J.E. et al. A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev. 26, 2392–2407 (2012). · DOI · Paper page
  28. Umekage, S., Uehara, T., Fujita, Y., Suzuki, H. & Kikuchi, Y. in Innovations in Biotechnology (ed. Agbo, E.C.) 75–90. http://cdn.intechopen.com/pdfs/28708/InTech-In_vivo_circular_rna_expression_by_the_permuted_intron_exon_method.pdf (InTech, 2012).
  29. Haupenthal, J., Baehr, C., Kiermayer, S., Zeuzem, S. & Piiper, A. Inhibition of RNAse A family enzymes prevents degradation and loss of silencing activity of siRNAs in serum. Biochem. Pharmacol. 71, 702–710 (2006). · DOI
  30. Li, X.F. & Lytton, J. A circularized sodium-calcium exchanger exon 2 transcript. J. Biol. Chem. 274, 8153–8160 (1999). · DOI
  31. Dubin, R.A., Kazmi, M.A. & Ostrer, H. Inverted repeats are necessary for circularization of the mouse testis Sry transcript. Gene 167, 245–248 (1995). · DOI
  32. Burd, C.E. et al. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet. 6, e1001233 (2010). · DOI · Paper page
  33. Pasman, Z., Been, M.D. & Garcia-Blanco, M.A. Exon circularization in mammalian nuclear extracts. RNA 2, 603–610 (1996).
  34. Ebert, M.S., Neilson, J.R. & Sharp, P.A. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat. Methods 4, 721–726 (2007). · DOI · Paper page
  35. Franco-Zorrilla, J.M. et al. Target mimicry provides a new mechanism for regulation of microRNA activity. Nat. Genet. 39, 1033–1037 (2007). · DOI · Paper page
  36. Poliseno, L. et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033–1038 (2010). · DOI · Paper page
  37. Hansen, T.B., Kjems, J. & Damgaard, C.K. Circular RNA and miR-7 in Cancer. Cancer Res. 73, 5609–5612 (2013). · DOI · Paper page
  38. Liu, Y. et al. Construction of circular miRNA sponges targeting miR-21 or miR-221 and demonstration of their excellent anticancer effects on malignant melanoma cells. Int. J. Biochem. Cell Biol. 45, 2643–2650 (2013). · DOI
  39. Chao, C.W., Chan, D.C., Kuo, A. & Leder, P. The mouse formin (Fmn) gene: abundant circular RNA transcripts and gene-targeted deletion analysis. Mol. Med. 4, 614–628 (1998). · DOI · Paper page
  40. Surono, A. et al. Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing. Hum. Mol. Genet. 8, 493–500 (1999). · DOI
  41. Gualandi, F. Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion. J. Med. Genet. 40, e100 (2003). · doi:10.1136/jmg.40.8.e100
  42. Spitali, P. & Aartsma-Rus, A. Splice modulating therapies for human disease. Cell 148, 1085–1088 (2012). · DOI
  43. Romeo, T. Global regulation by the small RNA-binding protein CsrA and the non-coding RNA molecule CsrB. Mol. Microbiol. 29, 1321–1330 (1998). · DOI · Paper page
  44. Chen, C.Y. & Sarnow, P. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268, 415–417 (1995). · DOI · Paper page
  45. Zaphiropoulos, P.G. Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Mol. Cell. Biol. 17, 2985–2993 (1997). · DOI · Paper page

Cited by

See all 2,702

Metadata

Authors
Jeck, W. R., & Sharpless, N. E.
Venue
Nature Biotechnology
Published
2014-05
Volume
32
Issue
5
Pages
453-461
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2017919052
Cited by
2,702
References
8
FWCI
35.53
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

About these checks

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Detecting and characterizing circular RNAs. https://app.cochat.ai/papers/10.1038/nbt.2890
The paper
Jeck, W. R., & Sharpless, N. E. (2014). Detecting and characterizing circular RNAs. Nature Biotechnology. https://doi.org/10.1038/nbt.2890

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.