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Detecting and characterizing circular RNAs

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.

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Figure 1: Splicing products and methods for detection.
Figure 2: Sequencing-based methods for identification of exonic circRNAs.
Figure 3: Informatic approach to identifying false-positive backsplices.
Figure 4: A combined biochemical and informatic approach to identify exonic circRNAs in mammalian cells.
Figure 5: Comparison of circRNAs identified by genomic studies.
Figure 6: Possible mechanisms for formation of exonic circRNAs.
Figure 7: Genomic features of circRNAs.

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Acknowledgements

The authors would like to acknowledge W. Marzluff for his assistance in preparing this manuscript, as well as funding from the National Institute on Aging, grants F30 AG041567–3 and RO1 AG024379–11.

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Correspondence to Norman E Sharpless.

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Jeck, W., Sharpless, N. Detecting and characterizing circular RNAs. Nat Biotechnol 32, 453–461 (2014). https://doi.org/10.1038/nbt.2890

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