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ADARs act as potent regulators of circular transcriptome in cancer
Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938519/ https://www.ncbi.nlm.nih.gov/pubmed/35314703 http://dx.doi.org/10.1038/s41467-022-29138-2 |
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author | Shen, Haoqing An, Omer Ren, Xi Song, Yangyang Tang, Sze Jing Ke, Xin-Yu Han, Jian Tay, Daryl Jin Tai Ng, Vanessa Hui En Molias, Fernando Bellido Pitcheshwar, Priyankaa Leong, Ka Wai Tan, Ker-Kan Yang, Henry Chen, Leilei |
author_facet | Shen, Haoqing An, Omer Ren, Xi Song, Yangyang Tang, Sze Jing Ke, Xin-Yu Han, Jian Tay, Daryl Jin Tai Ng, Vanessa Hui En Molias, Fernando Bellido Pitcheshwar, Priyankaa Leong, Ka Wai Tan, Ker-Kan Yang, Henry Chen, Leilei |
author_sort | Shen, Haoqing |
collection | PubMed |
description | Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis. |
format | Online Article Text |
id | pubmed-8938519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89385192022-04-08 ADARs act as potent regulators of circular transcriptome in cancer Shen, Haoqing An, Omer Ren, Xi Song, Yangyang Tang, Sze Jing Ke, Xin-Yu Han, Jian Tay, Daryl Jin Tai Ng, Vanessa Hui En Molias, Fernando Bellido Pitcheshwar, Priyankaa Leong, Ka Wai Tan, Ker-Kan Yang, Henry Chen, Leilei Nat Commun Article Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis. Nature Publishing Group UK 2022-03-21 /pmc/articles/PMC8938519/ /pubmed/35314703 http://dx.doi.org/10.1038/s41467-022-29138-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Shen, Haoqing An, Omer Ren, Xi Song, Yangyang Tang, Sze Jing Ke, Xin-Yu Han, Jian Tay, Daryl Jin Tai Ng, Vanessa Hui En Molias, Fernando Bellido Pitcheshwar, Priyankaa Leong, Ka Wai Tan, Ker-Kan Yang, Henry Chen, Leilei ADARs act as potent regulators of circular transcriptome in cancer |
title | ADARs act as potent regulators of circular transcriptome in cancer |
title_full | ADARs act as potent regulators of circular transcriptome in cancer |
title_fullStr | ADARs act as potent regulators of circular transcriptome in cancer |
title_full_unstemmed | ADARs act as potent regulators of circular transcriptome in cancer |
title_short | ADARs act as potent regulators of circular transcriptome in cancer |
title_sort | adars act as potent regulators of circular transcriptome in cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938519/ https://www.ncbi.nlm.nih.gov/pubmed/35314703 http://dx.doi.org/10.1038/s41467-022-29138-2 |
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