A guide to naming eukaryotic circular RNAs

Ling-Ling Chen¹, Albrecht Bindereif², Irene Bozzoni³, Howard Y Chang⁴, A Gregory Matera⁵, Myriam Gorospe⁶, Thomas B Hansen⁷, Jørgen Kjems⁷, Xu-Kai Ma⁸, Jun Wei Pek⁹, Nikolaus Rajewsky¹⁰, Julia Salzman¹¹, Jeremy E Wilusz¹², Li Yang¹³, Fangqing Zhao¹⁴

Affiliations

¹ State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. linglingchen@sibcb.ac.cn.
² Institute of Biochemistry, Faculty of Biology and Chemistry, Justus Liebig University of Giessen, Giessen, Germany.
³ Department of Biology and Biotechnologies 'Charles Darwin' and IIT Center for Life Nano- & Neuro-Science@Sapienza, Sapienza University of Rome, Rome, Italy.
⁴ Center for Personal Dynamic Regulomes, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
⁵ Integrative Program in Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
⁶ Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
⁷ Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
⁸ Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁹ Temasek Life Sciences Laboratory, 1 Research Link National University of Singapore, Singapore, Singapore.
¹⁰ Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Hemholtz Association, Berlin, Germany.
¹¹ Department of Biochemistry, Stanford University, Stanford, CA, USA.
¹² Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX, USA. jeremy.wilusz@bcm.edu.
¹³ Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. liyang_fudan@fudan.edu.cn.
¹⁴ Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.

PMID: 36658223
PMCID: PMC10114414
DOI: 10.1038/s41556-022-01066-9

A guide to naming eukaryotic circular RNAs

Ling-Ling Chen et al. Nat Cell Biol. 2023 Jan.

. 2023 Jan;25(1):1-5.

doi: 10.1038/s41556-022-01066-9.

Authors

Affiliations

¹ State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. linglingchen@sibcb.ac.cn.
² Institute of Biochemistry, Faculty of Biology and Chemistry, Justus Liebig University of Giessen, Giessen, Germany.
³ Department of Biology and Biotechnologies 'Charles Darwin' and IIT Center for Life Nano- & Neuro-Science@Sapienza, Sapienza University of Rome, Rome, Italy.
⁴ Center for Personal Dynamic Regulomes, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
⁵ Integrative Program in Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
⁶ Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
⁷ Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
⁸ Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁹ Temasek Life Sciences Laboratory, 1 Research Link National University of Singapore, Singapore, Singapore.
¹⁰ Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Hemholtz Association, Berlin, Germany.
¹¹ Department of Biochemistry, Stanford University, Stanford, CA, USA.
¹² Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX, USA. jeremy.wilusz@bcm.edu.
¹³ Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. liyang_fudan@fudan.edu.cn.
¹⁴ Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.

PMID: 36658223
PMCID: PMC10114414
DOI: 10.1038/s41556-022-01066-9

Abstract

Alternative splicing of eukaryotic transcripts often leads to production of multiple mature RNAs from a single gene locus. In addition to encoding linear RNAs, genes can produce stable circular RNAs (circRNAs) that are often co-expressed with their cognate linear RNAs. Multiple distinct circRNAs are frequently generated from a gene locus via back-splicing, with each mature transcript having a potentially unique function due to its distinct combination of exons and sometimes retained introns. However, names currently given to circRNAs are often ambiguous and lack consistency across studies. Here, we call on the community to embrace standards for naming circRNAs so that a common nomenclature is used to ensure clarity and reproducibility.

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Figures

**Figure 1.. Suggested naming scheme to clarify the complexity of circular RNA expression patterns.**
a. (Top) Pre-RNAs can be spliced to generate mature linear RNAs that are capped and polyadenylated as well as intron lariats that are debranched and degraded (denoted by dashed lines). However, some lariats fail to be debranched leading to the accumulation of stable ciRNAs. (Bottom) In addition to generating linear RNAs, a gene can generate circRNAs when a 5’ splice site (ss) is joined to an upstream 3’ ss via a process known as back-splicing. Of note, the efficiency of back-splicing (thin arrow) is often low compared with that of canonical splicing (heavy arrow) at the same gene locus. b. Naming of human circRNAs produced from the gene *FAM120A* (ENST00000277165.11) that have different BSJ sites. c. Naming of circRNAs produced from the gene *COX5A* (ENST00000322347.11) that have different BSJ sites. d. Naming of two alternative circRNAs produced from the gene *TIMMDC1* (ENST00000494664.6) that differ in their inclusion of a cassette exon. e. Naming of circRNAs produced from the gene *CAMSAP1* (ENST00000389532.9) that differ in their inclusion of a retained intron. f. Naming of circRNAs produced from the gene *MCU* (ENST00000603649.5) that differ in their use of an alternative 3’ ss. A longer exon 3 (L3) with additional sequence at the 5’-end of the annotated exon 3 can be alternatively spliced within the circRNA produced from the *MCU* gene locus. g. Naming of circRNAs produced from the gene *SNX25* (ENST00000618785.4) that differ in their use of an alternative 5’ ss. h. Naming of circRNAs produced from the gene *ZNF292* (ENST00000369578.6) that differ in their BSJ and presence of a novel exon. i. Naming of circRNAs produced from the gene *XPO1* (ENST00000401558.7) that differ in their inclusion of a novel cassette exon. j. Naming of fusion circRNAs produced from the *KMT2A::MLLT3* (also known as *MLL::AF9*) translocation in leukemic cell lines. Gene assembly: bars, exons; black lines, introns. Canonical splice junctions (SJs, polylines) and back-splice junctions (BSJs, arc lines) are shown in sequencing data. Short-read (purple) and long-read (orange) examples are shown.

None — **Naming of a ciRNA produced from an intron lariat.**
*ciANKRD52(2)* is produced from the second intron of the *ANKRD52* gene.

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References

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A guide to naming eukaryotic circular RNAs

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A guide to naming eukaryotic circular RNAs

Authors

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Abstract

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