Exon-intron circular RNAs regulate transcription in the nucleus
Abstract
Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression. A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA sponges in animal cells. Here, we report a class of circRNAs associated with RNA polymerase II in human cells. In these circRNAs, exons are circularized with introns 'retained' between exons; we term them exon-intron circRNAs or EIciRNAs. EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP and promote transcription of their parental genes. Our findings reveal a new role for circRNAs in regulating gene expression in the nucleus, in which EIciRNAs enhance the expression of their parental genes in cis, and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs.
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Three types of circRNAs have been reported: circular intronic RNAs (ciRNAs), retained-intron or exon-intron circRNAs (EIciRNAs), and intergenic circRNAs.
“Three types of circRNAs have been reported, which are produced via different molecular processes, including circular intronic RNAs (ciR-NAs), retained-intron or exon-intron circRNAs (EIciRNAs), and intergenic circRNAs [40,41] (Fig. 1).”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [41]
EIciRNAs promote gene transcription through interactions with U1 small nuclear RNAs (snRNAs) and RNA polymerase II (Pol II).
“EIciRNAs (a subclass of circRNAs) have been shown to promote gene transcription through interactions with U1 small nuclear RNAs (snRNAs) and RNA polymerase II (Pol II) [41].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [41]
CircRNAs may act as miRNA sponges by interacting with RBPs, and regulating mRNA transcription, splicing, and translation.
“CircRNAs may act as miRNA sponges by interacting with RBPs, and regulating mRNA transcription, splicing, and translation [14,41,51].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [41]
Cites
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400 · see citing works
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
Natural RNA circles function as efficient microRNA sponges
Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., & Kjems, J. (2013) · Nature · doi:10.1038/nature11993 · Cited by 7,985 · see citing works
Circular RNAs are abundant, conserved, and associated with ALU repeats
Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., Marzluff, W. F., & Sharpless, N. E. (2013) · RNA · doi:10.1261/rna.035667.112 · Cited by 4,388 · see citing works
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X. H., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P., Segal, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.022 · Cited by 4,246 · 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
lincRNAs: Genomics, Evolution, and Mechanisms
Ulitsky, I., & Bartel, D. P. (2013) · Cell · doi:10.1016/j.cell.2013.06.020 · Cited by 2,596 · see citing works
The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones
Cech, T. R., & Steitz, J. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.008 · Cited by 2,270 · 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
Self-citationComplementary 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
Self-citationCell-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
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
RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts
Geisler, S., & Coller, J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3679 · Cited by 1,451 · see citing works
Genomic Maps of Long Noncoding RNA Occupancy Reveal Principles of RNA-Chromatin Interactions
Chu, C., Qu, K., Zhong, F. L., Artandi, S. E., & Chang, H. Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.027 · Cited by 1,274 · see citing works
Epigenetic Regulation by Long Noncoding RNAs
Lee, J. T. (2012) · Science · doi:10.1126/science.1231776 · Cited by 1,258 · see citing works
Circular 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
Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells
HSU, M.-T., & COCA-PRADOS, M. (1979) · Nature · doi:10.1038/280339a0 · Cited by 1,021 · see citing works
RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond
Castel, S. E., & Martienssen, R. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3355 · Cited by 977 · 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
The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin
Nagano, T., Mitchell, J. A., Sanz, L. A., Pauler, F. M., Ferguson‐Smith, A. C., Feil, R., & Fraser, P. (2008) · Science · doi:10.1126/science.1163802 · Cited by 907 · see citing works
Nigro, 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
Activating RNAs associate with Mediator to enhance chromatin architecture and transcription
Lai, F., Ørom, U. A., Cesaroni, M., Beringer, M., Taatjes, D. J., Blobel, G. A., & Shiekhattar, R. (2013) · Nature · doi:10.1038/nature11884 · Cited by 857 · see citing works
Pre-mRNA Processing Reaches Back toTranscription and Ahead to Translation
Moore, M. J., & Proudfoot, N. J. (2009) · Cell · doi:10.1016/j.cell.2009.02.001 · Cited by 835 · see citing works
7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes
Nguyen, V. T., Kiss, T., Michels, A. A., & Bensaude, O. (2001) · Nature · doi:10.1038/35104581 · Cited by 708 · see citing works
Suzuki, H. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl151 · Cited by 687 · see citing works
The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
Yang, Z., Zhu, Q., Luo, K., et al. (2001) · Nature · doi:10.1038/35104575 · Cited by 681 · see citing works
U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
Kaida, D., Berg, M. G., Younis, I., Kasim, M., Singh, L. N., Wan, L., & Dreyfuss, G. (2010) · Nature · doi:10.1038/nature09479 · Cited by 638 · see citing works
Targeting nuclear RNA for in vivo correction of myotonic dystrophy
Wheeler, T. M., Leger, A. J., Pandey, S., MacLeod, A. R., Nakamori, M., Cheng, S. H., Wentworth, B. M., Bennett, C. F., & Thornton, C. A. (2012) · Nature · doi:10.1038/nature11362 · Cited by 503 · see citing works
U1 snRNP Determines mRNA Length and Regulates Isoform Expression
Berg, M. G., Singh, L. N., Younis, I., Liu, Q., Pinto, A. M., Kaida, D., Zhang, Z., Cho, S., Sherrill-Mix, S. A., Wan, L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.029 · Cited by 464 · see citing works
Promoter directionality is controlled by U1 snRNP and polyadenylation signals
Almada, A. E., Wu, X., Kriz, A. J., Burge, C. B., & Sharp, P. A. (2013) · Nature · doi:10.1038/nature12349 · Cited by 406 · see citing works
Wutz, A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3035 · Cited by 361 · see citing works
SR Proteins Collaborate with 7SK and Promoter-Associated Nascent RNA to Release Paused Polymerase
Ji, X., Zhou, Y., Pandit, S., Huang, J. S., Li, H., Lin, C. Y., Xiao, R., Burge, C. B., & Fu, X. (2013) · Cell · doi:10.1016/j.cell.2013.04.028 · Cited by 348 · see citing works
Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription
Guang, S., Bochner, A. F., Burkhart, K. B., et al. (2010) · Nature · doi:10.1038/nature09095 · Cited by 329 · see citing works
Splicing with inverted order of exons occurs proximal to large introns.
Cocquerelle, C., Daubersies, P., Majérus, M.-A., Kerckaert, J. P., & Bailleul, B. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05148.x · Cited by 314 · see citing works
Listerman, I., Sapra, A. K., & Neugebauer, K. M. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1135 · Cited by 309 · see citing works
Promoter proximal splice sites enhance transcriptionPreprint
Furger, A., O'Sullivan, A., Lee, B. A., & Proudfoot, N. J. (2002) · Genes & Development · doi:10.1101/gad.983602 · Cited by 276 · see citing works
Non-coding-RNA regulators of RNA polymerase II transcription
Goodrich, J. A., & Kugel, J. F. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1946 · Cited by 273 · see citing works
Non-coding RNA: a new frontier in regulatory biology
Fu, X. (2014) · National Science Review · doi:10.1093/nsr/nwu008 · Cited by 257 · see citing works
U1 snRNA associates with TFIIH and regulates transcriptional initiation
Kwek, K. Y., Murphy, S., Furger, A., Thomas, B., O'Gorman, W., Kimurâ, H., Proudfoot, N. J., & Akoulitchev, A. V. (2002) · Nature Structural Biology · doi:10.1038/nsb862 · Cited by 255 · see citing works
Luo, Y., Shan, G., Guo, W., Smrt, R. D., Johnson, E. B., Li, X., Pfeiffer, R. L., Szulwach, K. E., Duan, R., Barkho, B. Z., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000898 · Cited by 238 · see citing works
Self-citationA 5′ Splice Site Enhances the Recruitment of Basal Transcription Initiation Factors In Vivo
Damgaard, C. K., Kahns, S., Lykke‐Andersen, S., Nielsen, A. L., Jensen, T. H., & Kjems, J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.11.035 · Cited by 180 · 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
Escherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans
Liu, H., Wang, X., Wang, H., Wu, J., Ren, J., Meng, L., Wu, Q., Dong, H., Wu, J., Kao, T., et al. (2012) · Nature Communications · doi:10.1038/ncomms2071 · Cited by 133 · see citing works
Self-citationlinc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cisPreprint
Maamar, H., Cabili, M. N., Rinn, J. L., & Raj, A. (2013) · Genes & Development · doi:10.1101/gad.217018.113 · Cited by 124 · see citing works
Dixon, R. J. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki893 · Cited by 46 · 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
Signals from noncoding RNAs: unconventional roles for conventional pol III transcripts.
Hu, S., Wu, J., Chen, L., & Ge, S. (2012) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2012.07.013 · Cited by 37 · see citing works
Self-citationBioinformatic analysis of exon repetition, exon scrambling and trans-splicing in humans
Shao, X., Shepelev, V., & Fedorov, A. N. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti795 · Cited by 30 · see citing works
Modulation of chromatin modifying complexes by noncoding RNAs in trans
Názer, E., & Lei, E. P. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.019 · Cited by 15 · see citing works
Environmental RNA interference in animals
Meng, L., Chen, L., Li, Z., Wu, Z., & Shan, G. (2013) · Chinese Science Bulletin · doi:10.1007/s11434-013-5982-0 · Cited by 7 · see citing works
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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
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Chen, L.-L., & Yang, L. (2015) · RNA Biology · doi:10.1080/15476286.2015.1020271 · Cited by 1,953 · see citing works
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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
Pamudurti, N. R., Bartok, O., Jens, M., Ashwal-Fluss, R., Stottmeister, C., Ruhe, L., Hanan, M., Wyler, E., Perez-Hernandez, D., Ramberger, E., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.021 · Cited by 1,810 · see citing works
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Chen, L.-L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.32 · Cited by 1,743 · see citing works
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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
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- Authors
- Li, Z., Huang, C., Bao, C., Chen, L., Lin, M., Wang, X., Zhong, G., Yu, B., Hu, W., Dai, L., Zhu, P., Chang, Z., Wu, Q., Zhao, Y., Jia, Y., Xu, P., Liu, H., & Shan, G.
- Affiliations
- University of Science and Technology of China (CN)
- Chinese Academy of Sciences (CN)
- Central China Normal University (CN)
- Corresponding author
- Shan, Ge
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2015-02-09
- Volume
- 22
- Issue
- 3
- Pages
- 256-264
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W1966411071
- Cited by
- 2,905
- References
- 50
- Citations by year
- 2026: 130 · 2025: 196 · 2024: 276 · 2023: 275 · 2022: 380 · 2021: 447 · 2020: 410 · 2019: 302 · 2018: 234 · 2017: 138 · 2016: 72 · 2015: 37 · 2012: 1
- FWCI
- 69.54
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-02-01)
- Open access
- closed
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- 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, transcriptional regulation, RNA polymerase II, U1 snRNP, U1 snRNA, RNA-RNA interactions, cis-regulation, gene expression regulation, nuclear localization
- MeSH terms
- Base Sequence, Exons, Gene Expression Regulation, HeLa Cells, Humans, Introns, Models, Genetic, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, RNA Polymerase II, Sequence Analysis, RNA, RNA, Untranslated, HEK293 Cells
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