Circular RNAs are abundant, conserved, and associated with ALU repeats
Open accessAbstract
Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
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Two models of circRNA formation have been proposed: Lariat-Driven Circularization and Intron-Pairing-Driven Circularization.
“Two different models of circRNA formation have been proposed: an exon-skipping process known as “Lariat-Driven Circularization” and a nonsequential donor-acceptor pairing process called “Intron-Pairing-Driven Circularization” or “direct back splicing” [28].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [28]
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Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437 · see citing works
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
Non-coding RNAs in human disease
Esteller, M. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3074 · Cited by 4,825 · see citing works
Salzman, J., Gawad, C., Wang, P. L., Lacayo, N. J., & Brown, P. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030733 · Cited by 2,457 · see citing works
Argonaute2 is the catalytic engine of mammalian RNAi
Liu, J., Carmell, M. A., Rivas, F. V., Marsden, C. G., Thomson, J. M., Song, J.-J., Hammond, S. M., Joshua-Tor, L., & Hannon, G. J. (2004) · Science · doi:10.1126/science.1102513 · Cited by 2,353 · see citing works
Self-citationA coding-independent function of gene and pseudogene mRNAs regulates tumour biology
Poliseno, L., Salmena, L., Zhang, J., Carver, B. S., Haveman, W. J., & Pandolfi, P. P. (2010) · Nature · doi:10.1038/nature09144 · Cited by 2,313 · see citing works
Target mimicry provides a new mechanism for regulation of microRNA activity
Franco‐Zorrilla, J. M., Valli, A. A., Todesco, M., Mateos, I., Puga, M. I., Rubio‐Somoza, I., Leyva, A., Weigel, D., Garcı́a, J. A., & Paz‐Ares, J. (2007) · Nature Genetics · doi:10.1038/ng2079 · Cited by 2,074 · see citing works
The economics of ribosome biosynthesis in yeast
Warner, J. R. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01460-7 · Cited by 1,933 · see citing works
MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells
Ebert, M. S., Neilson, J. R., & Sharp, P. A. (2007) · Nature Methods · doi:10.1038/nmeth1079 · Cited by 1,845 · see citing works
Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs
Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., & Tuschl, T. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.07.007 · Cited by 1,718 · see citing works
Pre-mRNA splicing and human diseasePreprint
Faustino, N. A., & Cooper, T. A. (2003) · Genes & Development · doi:10.1101/gad.1048803 · Cited by 1,256 · see citing works
Mis-splicing yields circular RNA molecules.
Cocquerelle, C., Mascrez, B., Hétuin, D., & Bailleul, B. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.1.7678559 · Cited by 1,197 · see citing works
MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery
Wang, K., Singh, D., Zeng, Z., Coleman, S. J., Huang, Y., Savich, G. L., He, X., Mieczkowski, P., Grimm, S. A., Perou, C. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq622 · Cited by 1,193 · see citing works
Self-citationCircular transcripts of the testis-determining gene Sry in adult mouse testis
Capel, B., Swain, A., Nicolis, S. K., Hacker, A., Walter, M. A., Koopman, P. A., Goodfellow, P. N., & Lovell-Badge, R. H. (1993) · Cell · doi:10.1016/0092-8674(93)90279-y · Cited by 1,100 · see citing works
miRNA‐dependent gene silencing involving Ago2‐mediated cleavage of a circular antisense RNA
Hansen, T. B., Wiklund, E. D., Bramsen, J. B., Villadsen, S. B., Statham, A. L., Clark, S. J., & Kjems, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.359 · Cited by 996 · see citing works
Burd, C. E., Jeck, W. R., Liu, Y., Sanoff, H. K., Wang, Z., & Sharpless, N. E. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001233 · Cited by 895 · see citing works
Self-citationNigro, J. M., Cho, K. R., Fearon, E. R., Kern, S. E., Ruppert, J. M., Oliner, J., Kinzler, K. W., & Vogelstein, B. (1991) · Cell · doi:10.1016/0092-8674(91)90244-s · Cited by 888 · see citing works
Initiation of Protein Synthesis by the Eukaryotic Translational Apparatus on Circular RNAs
Chen, C.-Y., & Sarnow, P. (1995) · Science · doi:10.1126/science.7536344 · Cited by 766 · see citing works
Functional consequences of developmentally regulated alternative splicing
Kalsotra, A., & Cooper, T. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3052 · Cited by 729 · see citing works
Suzuki, H. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl151 · Cited by 687 · see citing works
Transcriptome-wide discovery of circular RNAs in Archaea
Danan, M., Schwartz, S., Edelheit, S., & Sorek, R. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1009 · Cited by 560 · see citing works
Genomewide characterization of non-polyadenylated RNAs
Yang, L. C., Duff, M. O., Graveley, B. R., Carmichael, G., & Chen, L. (2011) · Genome biology · doi:10.1186/gb-2011-12-2-r16 · Cited by 423 · see citing works
Human branch point consensus sequence is yUnAy
Gao, K., Masuda, A., Matsuura, T., & Ohno, K. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn073 · Cited by 284 · see citing works
The architecture of pre-mRNAs affects mechanisms of splice-site pairing
Fox-Walsh, K. L., Dou, Y., Lam, B. J., Hung, S., Baldi, P., & Hertel, K. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508489102 · Cited by 267 · see citing works
INK4a‐deficient human diploid fibroblasts are resistant to RAS‐induced senescence
Brookes, S., Rowe, J., Ruas, M., Llanos, S., Clark, P. A., Lomax, M., James, M. C., Vatcheva, R., Bates, S., Vousden, K. H., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf289 · Cited by 220 · see citing works
Exon circularization in mammalian nuclear extracts.
Pasman, Z., Been, M. D., & García-Blanco, M. A. (1996) · PubMed · Cited by 185 · see citing works
Zaphiropoulos, P. G. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.2985 · Cited by 177 · see citing works
Inverted repeats are necessary for circularization of the mouse testis Sry transcript
Dubin, R. A., Kazmi, M. A., & D, H. O. M. (1995) · Gene · doi:10.1016/0378-1119(95)00639-7 · Cited by 154 · see citing works
Exhaustive Search for Over-represented DNA Sequence Motifs with CisFinder
Sharov, A. A., & Ko, M. S. H. (2009) · DNA Research · doi:10.1093/dnares/dsp014 · Cited by 130 · see citing works
Isono, K., Mizutani-Koseki, Y., Komori, T., Schmidt-Zachmann, M. S., & Koseki, H. (2005) · Genes & Development · doi:10.1101/gad.1284605 · Cited by 110 · see citing works
Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae
Hurowitz, E. H., & Brown, P. O. (2003) · Genome biology · doi:10.1186/gb-2003-5-1-r2 · Cited by 109 · see citing works
Alternative splicing in multiple sclerosis and other autoimmune diseases
Evsyukova, I. Y., Somarelli, J. A., Gregory, S. G., & García-Blanco, M. A. (2010) · RNA Biology · doi:10.4161/rna.7.4.12301 · Cited by 81 · see citing works
Ganguly, A. A., Dunbar, T., Chen, P., Godmilow, L., & Ganguly, T. (2003) · Human Genetics · doi:10.1007/s00439-003-0986-5 · Cited by 80 · see citing works
Reverse transcriptase reads through a 2′–5′ linkage and a 2′-thiphosphate in a template
Lorsch, J. R., Bartel, D. P., & Szostak, J. W. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.15.2811 · Cited by 69 · see citing works
Post-transcriptional exon shuffling events in humans can be evolutionarily conserved and abundantPreprint
Al‐Balool, H. H., Weber, D., Liu, Y., Wade, M., Guleria, K., Nam, P. L. P., Clayton, J., Rowe, W. P. M., Coxhead, J. M., Irving, J. A. E., et al. (2011) · Genome Research · doi:10.1101/gr.116442.110 · Cited by 46 · see citing works
Spliceosomes walk the line: Splicing errors and their impact on cellular function
Hsu, S.-N., & Hertel, K. J. (2009) · RNA Biology · doi:10.4161/rna.6.5.9860 · Cited by 34 · see citing works
Mutations in RNA Splicing Machinery in Human Cancers
Ebert, B. L., & Bernard, O. (2011) · New England Journal of Medicine · doi:10.1056/nejme1111584 · Cited by 25 · see citing works
Virtual Northern Analysis of the Human Genome
Hurowitz, E. H., Drori, I., Stodden, V., Donoho, D. L., & Brown, P. O. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000460 · Cited by 12 · see citing works
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Circular RNAs are a large class of animal RNAs with regulatory potency
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., et al. (2013) · Nature · doi:10.1038/nature11928 · Cited by 7,990 · see citing works
The biogenesis, biology and characterization of circular RNAs
Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0158-7 · Cited by 4,823 · see citing works
The multilayered complexity of ceRNA crosstalk and competition
Tay, Y., Rinn, J., & Pandolfi, P. P. (2014) · Nature · doi:10.1038/nature12986 · Cited by 3,910 · see citing works
Unique features of long non-coding RNA biogenesis and function
Quinn, J. J., & Chang, H. Y. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.10 · Cited by 3,653 · see citing works
circRNA biogenesis competes with pre-mRNA splicing
Ashwal-Fluss, R., Meyer, M., Pamudurti, N. R., Ivanov, A., Bartok, O., Hanan, M., Evantal, N., Memczak, S., Rajewsky, N., & Kadener, S. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.019 · Cited by 3,083 · see citing works
Exon-intron circular RNAs regulate transcription in the nucleus
Li, Z., Huang, C., Bao, C., Chen, L., Lin, M., Wang, X., Zhong, G., Yu, B., Hu, W., Dai, L., et al. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2959 · Cited by 2,905 · see citing works
Detecting and characterizing circular RNAs
Jeck, W. R., & Sharpless, N. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2890 · Cited by 2,685 · see citing works
Self-citationCircular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., Hanan, M., Behm, M., Bartok, O., Ashwal-Fluss, R., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.03.027 · Cited by 2,423 · see citing works
Circular intronic long noncoding RNAs
Zhang, Y., Zhang, X.-O., Chen, T., Xiang, J.-F., Yin, Q.-F., Xing, Y.-H., Zhu, S., Yang, L., & Chen, L.-L. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.017 · Cited by 2,221 · see citing works
Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis
Li, Y., Zheng, Q., Bao, C., Li, S., Guo, W., Zhao, J., Chen, D., Gu, J., He, X., & Huang, S. (2015) · Cell Research · doi:10.1038/cr.2015.82 · Cited by 2,210 · see citing works
Endogenous microRNA sponges: evidence and controversy
Thomson, D. W., & Dinger, M. E. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.20 · Cited by 1,833 · see citing works
The RNA Binding Protein Quaking Regulates Formation of circRNAs
Conn, S. J., Pillman, K. A., Toubia, J., Conn, V. M., Salmanidis, M., Phillips, C. A., Roslan, S., SCHREIBER, A. W., Gregory, P. A., & Goodall, G. J. (2015) · Cell · doi:10.1016/j.cell.2015.02.014 · Cited by 2,187 · see citing works
Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis
Legnini, I., Di Timoteo, G., Rossi, F., Morlando, M., Briganti, F., Sthandier, O., Fatica, A., Santini, T., Andronache, A., Wade, M., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.017 · Cited by 2,173 · see citing works
The Biogenesis, Functions, and Challenges of Circular RNAs
Li, X., Yang, L. C., & Chen, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.034 · Cited by 2,043 · see citing works
Zheng, Q., Bao, C., Guo, W., Li, S., Chen, J., Chen, B., Luo, Y., Lyu, D., Li, Y., Shi, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms11215 · Cited by 2,045 · see citing works
Complementary Sequence-Mediated Exon Circularization
Zhang, X.-O., Wang, H.-B., Zhang, Y., Lu, X., Chen, L.-L., & Yang, L. (2014) · Cell · doi:10.1016/j.cell.2014.09.001 · Cited by 1,999 · see citing works
Cell-Type Specific Features of Circular RNA Expression
Salzman, J., Chen, R. E., Olsen, M. N., Wang, P. L., & Brown, P. O. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003777 · Cited by 1,955 · see citing works
Regulation of circRNA biogenesis
Chen, L.-L., & Yang, L. (2015) · RNA Biology · doi:10.1080/15476286.2015.1020271 · Cited by 1,953 · see citing works
circBase: a database for circular RNAs
Glažar, P., Papavasileiou, P., & Rajewsky, N. (2014) · RNA · doi:10.1261/rna.043687.113 · Cited by 1,934 · see citing works
Extensive translation of circular RNAs driven by N6-methyladenosine
Yang, Y., Fan, X., Mao, M., Song, X., Wu, P., Zhang, Y., Jin, Y., Yang, Y., Chen, L.-L., Wang, Y., et al. (2017) · Cell Research · doi:10.1038/cr.2017.31 · Cited by 1,855 · see citing works
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 · see citing works
The Landscape of Circular RNA in Cancer
Vo, J. N., Cieslik, M. P., Zhang, Y., Shukla, S. K., Xiao, L., Zhang, Y., Wu, Y., Dhanasekaran, S. M., Engelke, C. G., Cao, X., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.021 · Cited by 1,746 · see citing works
The biogenesis and emerging roles of circular RNAs
Chen, L.-L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.32 · Cited by 1,743 · see citing works
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches
Beermann, J., Piccoli, M.-T., Viereck, J., & Thum, T. (2016) · Physiological Reviews · doi:10.1152/physrev.00041.2015 · Cited by 1,727 · see citing works
The expanding regulatory mechanisms and cellular functions of circular RNAs
Chen, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0243-y · Cited by 1,714 · see citing works
The role of non-coding RNAs in oncology
Slack, F. J., & Chinnaiyan, A. M. (2019) · Cell · doi:10.1016/j.cell.2019.10.017 · Cited by 1,619 · see citing works
Expanded identification and characterization of mammalian circular RNAs
Guo, J. U., Agarwal, V., Guo, H., & Bartel, D. P. (2014) · Genome biology · doi:10.1186/s13059-014-0409-z · Cited by 1,578 · see citing works
LNCcation: lncRNA localization and function
Bridges, M. C., Daulagala, A. C., & Kourtidis, A. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202009045 · Cited by 1,556 · see citing works
CircRNA: functions and properties of a novel potential biomarker for cancer
Meng, S., Zhou, H., Feng, Z., Xu, Z., Tang, Y., Li, P., & Wu, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0663-2 · Cited by 1,523 · see citing works
Circular RNA: metabolism, functions and interactions with proteins
Zhou, W.-Y., Cai, Z., Liu, J., Wang, D., Ju, H., & Xu, R. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01286-3 · Cited by 1,437 · see citing works
Self-citationCircular RNAs in cancer: opportunities and challenges in the field
Kristensen, L. S., Hansen, T. B., Venø, M. T., & Kjems, J. (2017) · Oncogene · doi:10.1038/onc.2017.361 · Cited by 1,328 · see citing works
The emerging roles of circRNAs in cancer and oncology
Kristensen, L. S., Jakobsen, T., Hager, H., & Kjems, J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00585-y · Cited by 1,256 · see citing works
CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs
Dudekula, D. B., Panda, A. C., Grammatikakis, I., De, S., Abdelmohsen, K., & Gorospe, M. (2015) · RNA Biology · doi:10.1080/15476286.2015.1128065 · Cited by 1,241 · see citing works
Past, present, and future of circRNAs
Patop, I. L., Wüst, S., & Kadener, S. (2019) · The EMBO Journal · doi:10.15252/embj.2018100836 · Cited by 1,228 · see citing works
Han, D., Li, J., Wang, H., Su, X., Hou, J., Gu, Y., Qian, C., Lin, Y., Liu, X., Huang, M., et al. (2017) · Hepatology · doi:10.1002/hep.29270 · Cited by 1,211 · see citing works
Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function
Piwecka, M., Glažar, P., Hernandez-Miranda, L. R., Memczak, S., Wolf, S. A., Rybak-Wolf, A., Filipchyk, A., Klironomos, F., Cerda Jara, C. A., Fenske, P., et al. (2017) · Science · doi:10.1126/science.aam8526 · Cited by 1,210 · see citing works
Circular RNAs: diversity of form and function
Lasda, E. L., & Parker, R. (2014) · RNA · doi:10.1261/rna.047126.114 · Cited by 1,193 · see citing works
The Landscape of long noncoding RNA classification
Laurent, G. S., Wahlestedt, C., & Kapranov, P. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.007 · Cited by 1,192 · see citing works
Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity
You, X., Vlatkovic, I., Babic, A., Will, T., Epstein, I., Tushev, G., Akbalik, G., Wang, M., Glock, C., Quedenau, C., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3975 · Cited by 1,149 · see citing works
Circular RNAs Act as miRNA Sponges
Panda, A. C. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1426-1_6 · Cited by 1,116 · see citing works
CIRI: an efficient and unbiased algorithm for de novo circular RNA identification
Gao, Y., Wang, J., & Zhao, F. (2015) · Genome biology · doi:10.1186/s13059-014-0571-3 · Cited by 1,118 · see citing works
Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis
Yang, Y., Gao, X., Zhang, M., Yan, S., Sun, C., Xiao, F., Huang, N., Yang, X., Zhao, K., Zhou, H., et al. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx166 · Cited by 1,108 · see citing works
Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals
Ivanov, A., Memczak, S., Wyler, E., Torti, F., Porath, H. T., Orejuela, M. R., Piechotta, M., Levanon, E. Y., Landthaler, M., Dieterich, C., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.12.019 · Cited by 1,092 · see citing works
Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans
Holdt, L. M., Stahringer, A., Sass, K., Pichler, G., Kulak, N. A., Wilfert, W., Kohlmaier, A., Herbst, A., Northoff, B. H., Nicolaou, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms12429 · Cited by 1,097 · see citing works
Circular RNAs: Characterization, cellular roles, and applications
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Goodall, G. J., & Wickramasinghe, V. O. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-00306-0 · Cited by 1,070 · see citing works
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Chan, J. J., & Tay, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051310 · Cited by 1,030 · see citing works
Diverse alternative back-splicing and alternative splicing landscape of circular RNAsPreprint
Zhang, X.-O., Dong, R., Zhang, Y., Zhang, J., Luo, Z. D., Zhang, J., Chen, L., & Yang, L. C. (2016) · Genome Research · doi:10.1101/gr.202895.115 · Cited by 1,022 · see citing works
Westholm, J. O., Miura, P., Olson, S., Shenker, S., Joseph, B. J., Sanfilippo, P., Celniker, S., Graveley, B. R., & Lai, E. C. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.062 · Cited by 1,001 · see citing works
Short intronic repeat sequences facilitate circular RNA productionPreprint
Liang, D., & Wilusz, J. E. (2014) · Genes & Development · doi:10.1101/gad.251926.114 · Cited by 959 · see citing works
Circular RNA-protein interactions: functions, mechanisms, and identification
Huang, A., Zheng, H., Wu, Z., Chen, M., & Huang, Y. (2020) · Theranostics · doi:10.7150/thno.42174 · Cited by 905 · see citing works
Non-coding RNA: what is functional and what is junk?
Palazzo, A. F., & Lee, E. S. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00002 · Cited by 891 · see citing works
Wang, K., Long, B., Liu, F., Wang, J., Liu, C.-Y., Zhao, B., Zhou, L., Sun, T., Wang, M., Yu, T., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv713 · Cited by 868 · see citing works
Self-citationHistory, Discovery, and Classification of lncRNAs
Jarroux, J., Morillon, A., & Pinskaya, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-5203-3_1 · Cited by 873 · see citing works
Circular RNAs: analysis, expression and potential functions
Barrett, S. P., & Salzman, J. (2016) · Development · doi:10.1242/dev.128074 · Cited by 859 · see citing works
Abdelmohsen, K., Panda, A. C., Munk, R., Grammatikakis, I., Dudekula, D. B., De, S., Kim, J., Noh, J. H., Kim, K. M., Martindale, J. L., et al. (2017) · RNA Biology · doi:10.1080/15476286.2017.1279788 · Cited by 858 · see citing works
ceRNA Cross-Talk in Cancer: When ce-bling Rivalries Go Awry
Karreth, F. A., & Pandolfi, P. P. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0202 · Cited by 851 · see citing works
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 · see citing works
Circular RNA Expression: Its Potential Regulation and Function
Salzman, J. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.03.002 · Cited by 805 · see citing works
Circular RNAs in Cancer: Biogenesis, Function, and Clinical Significance
Li, J., Sun, D., Pu, W., Wang, J., & Peng, Y. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.01.012 · Cited by 797 · see citing works
Circular RNA and its mechanisms in disease: From the bench to the clinic
Han, B., Chao, J., & Yao, H. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.01.010 · Cited by 784 · see citing works
Exon Circularization Requires Canonical Splice Signals
Starke, S., Jost, I., Roßbach, O., Schneider, T. P., Schreiner, S., Hung, L.-H., & Bindereif, A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.12.002 · Cited by 768 · see citing works
Circular RNAs: Promising Biomarkers for Human Diseases
Zhang, Z., Yang, T., & Xiao, J. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.07.036 · Cited by 776 · see citing works
Using circular RNA as a novel type of biomarker in the screening of gastric cancer
Li, P., Chen, S., Chen, H., Mo, X., Li, T., Shao, Y., Xiao, B., & Guo, J. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.02.018 · Cited by 773 · see citing works
Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma
Yu, J., Xu, Q., Wang, Z., Yang, Y., Zhang, L., Ma, J., Sun, S., Yang, F., & Zhou, W. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.01.012 · Cited by 763 · see citing works
CircRNA: a novel type of biomarker for cancer
Zhang, H.-D., Jiang, L., Sun, D., Hou, J., & Ji, Z. (2017) · Breast Cancer · doi:10.1007/s12282-017-0793-9 · Cited by 761 · see citing works
Enuka, Y., Lauriola, M., Feldman, M. E., Sas-Chen, A., Ulitsky, I., & Yarden, Y. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1367 · Cited by 757 · see citing works
Circular RNA Is Expressed across the Eukaryotic Tree of Life
Wang, P. L., Bao, Y., Yee, M., Barrett, S. P., Hogan, G. J., Olsen, M. N., Dinneny, J. R., Brown, P. O., & Salzman, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090859 · Cited by 754 · see citing works
Long Noncoding RNAs in Cardiovascular Diseases
Uchida, S., & Dimmeler, S. (2015) · Circulation Research · doi:10.1161/circresaha.116.302521 · Cited by 739 · see citing works
Zhang, M., Zhao, K., Xu, X., Yang, Y., Yan, S., Wei, P., Liu, H., Xu, J., Xiao, F., Zhou, H., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06862-2 · Cited by 737 · see citing works
Self-citationCircular RNAs are miRNA sponges and can be used as a new class of biomarker
Kulcheski, F. R., Christoff, A. P., & Margis, R. (2016) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2016.09.011 · Cited by 739 · see citing works
Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal Translocations
Guarnerio, J., Bezzi, M., Jeong, J. C., Paffenholz, S. V., Berry, K., Naldini, M. M., Lo‐Coco, F., Tay, Y., Beck, A. H., & Pandolfi, P. P. (2016) · Cell · doi:10.1016/j.cell.2016.03.020 · Cited by 739 · see citing works
Bachmayr-Heyda, A., Reiner, A. T., Auer, K., Sukhbaatar, N., Aust, S., Bachleitner‐Hofmann, T., Mesteri, I., Grunt, T. W., Zeillinger, R., & Pils, D. (2015) · Scientific Reports · doi:10.1038/srep08057 · Cited by 732 · see citing works
Chen, R., Chen, X., Xia, L., Zhang, J., Pan, Z., Ma, X.-D., Han, K., Chen, J., Judde, J.-G., Déas, O., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12651-2 · Cited by 736 · see citing works
A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis
Zhang, M., Huang, N., Yang, X., Luo, J., Yan, S., Xiao, F., Chen, W., Gao, X., Zhao, K., Zhou, H., et al. (2018) · Oncogene · doi:10.1038/s41388-017-0019-9 · Cited by 723 · see citing works
Circular RNA identification based on multiple seed matching
Gao, Y., Zhang, J., & Zhao, F. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbx014 · Cited by 703 · see citing works
Gene regulation in the immune system by long noncoding RNAs
Chen, Y. G., Satpathy, A. T., & Chang, H. Y. (2017) · Nature Immunology · doi:10.1038/ni.3771 · Cited by 686 · see citing works
Non-Coding RNAs and their Integrated Networks
Zhang, P., Wu, W., Chen, Q., & Chen, M. (2019) · Berichte aus der medizinischen Informatik und Bioinformatik/Journal of integrative bioinformatics · doi:10.1515/jib-2019-0027 · Cited by 691 · see citing works
Chen, J., Li, Y., Zheng, Q., Bao, C., He, J. G., Chen, B., Lyu, D., Zheng, B., Xu, Y., Long, Z., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.12.006 · Cited by 686 · see citing works
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 · see citing works
Efficient backsplicing produces translatable circular mRNAs
Wang, Y., & Wang, Z. (2014) · RNA · doi:10.1261/rna.048272.114 · Cited by 665 · see citing works
Functional interactions among microRNAs and long noncoding RNAs
Yoon, J., Abdelmohsen, K., & Gorospe, M. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.05.015 · Cited by 658 · see citing works
The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva
Bahn, J. H., Zhang, Q., Li, F., Chan, T.-M., Lin, X., Kim, Y. D., Wong, D. T., & Xiao, X. G. (2014) · Clinical Chemistry · doi:10.1373/clinchem.2014.230433 · Cited by 658 · see citing works
The Biogenesis of Nascent Circular RNAs
Zhang, Y., Xue, W., Li, X., Zhang, J., Chen, S., Zhang, J.-L., Yang, L., & Chen, L.-L. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.058 · Cited by 643 · see citing works
MicroRNAs and complex diseases: from experimental results to computational models
Chen, X., Xie, D., Zhao, Q., & You, Z. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbx130 · Cited by 640 · see citing works
Memczak, S., Papavasileiou, P., Peters, O., & Rajewsky, N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141214 · Cited by 639 · see citing works
Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway
Li, F., Zhang, L.-Y., Li, W., Deng, J., Zheng, J., An, M., Lu, J.-C., & Zhou, Y.-F. (2015) · OncoTarget · doi:10.18632/oncotarget.3469 · Cited by 669 · see citing works
RETRACTED ARTICLE: CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7
Zeng, K., Chen, X., Xu, M., Liu, X., Hu, X., Xu, T., Sun, H., Pan, Y., He, B., & Wang, S. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0454-8 · Cited by 628 · see citing works
RetractedSzabo, L. A., Morey, R. E., Palpant, N. J., Wang, P. L., Afari, N., Chuan, J., Parast, M. M., Murry, C. E., Laurent, L. C., & Salzman, J. (2015) · Genome biology · doi:10.1186/s13059-015-0690-5 · Cited by 608 · see citing works
DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome
Aktaş, T., Ilik, İ., Maticzka, D., Bhardwaj, V., Rodrigues, C. P., Mittler, G., Manke, T., Backofen, R., & Akhtar, A. (2017) · Nature · doi:10.1038/nature21715 · Cited by 594 · see citing works
Circular RNAs: Identification, biogenesis and function
Ebbesen, K. K., Kjems, J., & Hansen, T. B. (2015) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2015.07.007 · Cited by 558 · see citing works
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 559 · see citing works
Targeting circular RNAs as a therapeutic approach: current strategies and challenges
He, A. T., Liu, J., Li, F., & Yang, B. B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00569-5 · Cited by 556 · see citing works
Self-citationCircular RNAs: Biogenesis, Function and Role in Human Diseases
Greene, J. P., Baird, A., Brady, L., Lim, M. C. J., Gray, S. G., McDermott, R., & Finn, S. P. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00038 · Cited by 554 · see citing works
The novel roles of circRNAs in human cancer
Shang, Q., Yang, Z. H., Jia, R., & Ge, S. (2019) · Molecular Cancer · doi:10.1186/s12943-018-0934-6 · Cited by 548 · see citing works
Widespread and Functional RNA Circularization in Localized Prostate Cancer
Chen, S., Huang, V., Xu, X., Livingstone, J., Soares, F., Jeon, J., Zeng, Y., Hua, J. T., Petricca, J., Guo, H., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.025 · Cited by 544 · see citing works
FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
Errichelli, L., Modigliani, S. D., Laneve, P., Colantoni, A., Legnini, I., Capauto, D., Rosa, A., Santis, R. D., Scarfò, R., Peruzzi, G., et al. (2017) · Nature Communications · doi:10.1038/ncomms14741 · Cited by 541 · see citing works
CircRNA in cancer: Fundamental mechanism and clinical potential
Chen, L., & Shan, G. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.02.004 · Cited by 540 · see citing works
Xu, H., Guo, S., Li, W., & Yu, P. (2015) · Scientific Reports · doi:10.1038/srep12453 · Cited by 529 · see citing works
[Retracted] Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures
Kashyap, D., Pal, D., Sharma, R., Garg, V. K., Goel, N., Koundal, D., Zaguia, A., Koundal, S., & Belay, A. (2022) · BioMed Research International · doi:10.1155/2022/9605439 · Cited by 565 · see citing works
Retracted
- Authors
- Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., Marzluff, W. F., & Sharpless, N. E.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Kentucky (US)
- ORCID
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-12-18
- Volume
- 19
- Issue
- 2
- Pages
- 141-157
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC3543092
- OpenAlex
- W2147806662
- Cited by
- 4,388
- References
- 41
- Citations by year
- 2026: 165 · 2025: 251 · 2024: 369 · 2023: 409 · 2022: 566 · 2021: 655 · 2020: 612 · 2019: 467 · 2018: 369 · 2017: 227 · 2016: 121 · 2015: 92 · 2014: 47 · 2013: 31 · 2012: 1
- FWCI
- 22.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- UNC Libraries
- Funders
- Glenn Foundation for Medical Research
- National Institutes of Health (5r01ag024379-15)
- National Institute on Aging (AG024379, AG041567, R01-AG024379, F30AG041567)
- National Human Genome Research Institute (R01HG006272)
- National Institute of General Medical Sciences (F32GM087059, T32GM007092)
- National Institute of Environmental Health Sciences (T32ES007126)
- 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 › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- circular RNA, back-splicing, Alu elements, RNase R, human fibroblasts, mouse testis, HIPK2, HIPK3, competing endogenous RNA, RNA stability, gene expression regulation
- MeSH terms
- RNA, Circular, Animals, Base Sequence, Cells, Cultured, Exons, Exoribonucleases, Gene Expression Regulation, Humans, Male, Molecular Sequence Data, Phosphotransferases, RNA, RNA Splicing, Conserved Sequence, Sequence Analysis, RNA, Evolution, Molecular, Computational Biology, Trans-Splicing, Alu Elements, RNA Stability, RNA, Small Interfering, Mice, High-Throughput Nucleotide Sequencing, Nucleotide Motifs
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