Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals
Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human ALU repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified circRNAs in C. eleg...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-01-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714010481 |
| _version_ | 1811269652869808128 |
|---|---|
| author | Andranik Ivanov Sebastian Memczak Emanuel Wyler Francesca Torti Hagit T. Porath Marta R. Orejuela Michael Piechotta Erez Y. Levanon Markus Landthaler Christoph Dieterich Nikolaus Rajewsky |
| author_facet | Andranik Ivanov Sebastian Memczak Emanuel Wyler Francesca Torti Hagit T. Porath Marta R. Orejuela Michael Piechotta Erez Y. Levanon Markus Landthaler Christoph Dieterich Nikolaus Rajewsky |
| author_sort | Andranik Ivanov |
| collection | DOAJ |
| description | Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human ALU repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched in comparison to linear controls. By scoring the presence of reverse complementary sequences in human introns, we predicted and experimentally validated circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyperediting events. Knockdown of the double-strand RNA-editing enzyme ADAR1 significantly and specifically upregulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA-RNA interactions of introns form larger structures that promote circularization of embedded exons, whereas ADAR1 antagonizes circRNA expression by melting stems within these interactions. |
| first_indexed | 2024-04-12T21:46:54Z |
| format | Article |
| id | doaj.art-c91cfa89a3db4f71a43ef062808a8763 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T21:46:54Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c91cfa89a3db4f71a43ef062808a87632022-12-22T03:15:37ZengElsevierCell Reports2211-12472015-01-0110217017710.1016/j.celrep.2014.12.019Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in AnimalsAndranik Ivanov0Sebastian Memczak1Emanuel Wyler2Francesca Torti3Hagit T. Porath4Marta R. Orejuela5Michael Piechotta6Erez Y. Levanon7Markus Landthaler8Christoph Dieterich9Nikolaus Rajewsky10Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyLaboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, IsraelLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyMax Planck Institute for Biology of Ageing, Cologne, Joseph Stelzmann Straße 9B, 50931 Köln, GermanyThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, IsraelLaboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyMax Planck Institute for Biology of Ageing, Cologne, Joseph Stelzmann Straße 9B, 50931 Köln, GermanyLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Robert Roessle Straße 10, 13125 Berlin-Buch, GermanyCircular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human ALU repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched in comparison to linear controls. By scoring the presence of reverse complementary sequences in human introns, we predicted and experimentally validated circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyperediting events. Knockdown of the double-strand RNA-editing enzyme ADAR1 significantly and specifically upregulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA-RNA interactions of introns form larger structures that promote circularization of embedded exons, whereas ADAR1 antagonizes circRNA expression by melting stems within these interactions.http://www.sciencedirect.com/science/article/pii/S2211124714010481 |
| spellingShingle | Andranik Ivanov Sebastian Memczak Emanuel Wyler Francesca Torti Hagit T. Porath Marta R. Orejuela Michael Piechotta Erez Y. Levanon Markus Landthaler Christoph Dieterich Nikolaus Rajewsky Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals Cell Reports |
| title | Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals |
| title_full | Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals |
| title_fullStr | Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals |
| title_full_unstemmed | Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals |
| title_short | Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals |
| title_sort | analysis of intron sequences reveals hallmarks of circular rna biogenesis in animals |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714010481 |
| work_keys_str_mv | AT andranikivanov analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT sebastianmemczak analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT emanuelwyler analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT francescatorti analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT hagittporath analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT martarorejuela analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT michaelpiechotta analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT erezylevanon analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT markuslandthaler analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT christophdieterich analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals AT nikolausrajewsky analysisofintronsequencesrevealshallmarksofcircularrnabiogenesisinanimals |