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An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer

Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3′ untranslated regions (3′UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target g...

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Autores principales: Qi, Lihua, Song, Yangyang, Chan, Tim Hon Man, Yang, Henry, Lin, Chi Ho, Tay, Daryl Jin Tai, Hong, HuiQi, Tang, Sze Jing, Tan, Kar Tong, Huang, Xi Xiao, Lin, Jaymie Siqi, Ng, Vanessa Hui En, Maury, Julien Jean Pierre, Tenen, Daniel G., Chen, Leilei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737565/
https://www.ncbi.nlm.nih.gov/pubmed/28985428
http://dx.doi.org/10.1093/nar/gkx667
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author Qi, Lihua
Song, Yangyang
Chan, Tim Hon Man
Yang, Henry
Lin, Chi Ho
Tay, Daryl Jin Tai
Hong, HuiQi
Tang, Sze Jing
Tan, Kar Tong
Huang, Xi Xiao
Lin, Jaymie Siqi
Ng, Vanessa Hui En
Maury, Julien Jean Pierre
Tenen, Daniel G.
Chen, Leilei
author_facet Qi, Lihua
Song, Yangyang
Chan, Tim Hon Man
Yang, Henry
Lin, Chi Ho
Tay, Daryl Jin Tai
Hong, HuiQi
Tang, Sze Jing
Tan, Kar Tong
Huang, Xi Xiao
Lin, Jaymie Siqi
Ng, Vanessa Hui En
Maury, Julien Jean Pierre
Tenen, Daniel G.
Chen, Leilei
author_sort Qi, Lihua
collection PubMed
description Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3′ untranslated regions (3′UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3′UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3′UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3′UTR to repress its expression level. In sum, our study unveils that the extensive 3′UTR editing of METTL7A is merely a footprint of ADAR binding, and there are a subset of target genes that are equivalently regulated by ADAR1 and ADAR2 through their non-canonical RNA editing and dsRNA binding-independent functions, albeit maybe less common. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of high biological importance beyond the best-studied editing function. This non-editing side of ADARs opens another door to target cancer.
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spelling pubmed-57375652018-01-09 An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer Qi, Lihua Song, Yangyang Chan, Tim Hon Man Yang, Henry Lin, Chi Ho Tay, Daryl Jin Tai Hong, HuiQi Tang, Sze Jing Tan, Kar Tong Huang, Xi Xiao Lin, Jaymie Siqi Ng, Vanessa Hui En Maury, Julien Jean Pierre Tenen, Daniel G. Chen, Leilei Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3′ untranslated regions (3′UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3′UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3′UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3′UTR to repress its expression level. In sum, our study unveils that the extensive 3′UTR editing of METTL7A is merely a footprint of ADAR binding, and there are a subset of target genes that are equivalently regulated by ADAR1 and ADAR2 through their non-canonical RNA editing and dsRNA binding-independent functions, albeit maybe less common. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of high biological importance beyond the best-studied editing function. This non-editing side of ADARs opens another door to target cancer. Oxford University Press 2017-10-13 2017-07-29 /pmc/articles/PMC5737565/ /pubmed/28985428 http://dx.doi.org/10.1093/nar/gkx667 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Qi, Lihua
Song, Yangyang
Chan, Tim Hon Man
Yang, Henry
Lin, Chi Ho
Tay, Daryl Jin Tai
Hong, HuiQi
Tang, Sze Jing
Tan, Kar Tong
Huang, Xi Xiao
Lin, Jaymie Siqi
Ng, Vanessa Hui En
Maury, Julien Jean Pierre
Tenen, Daniel G.
Chen, Leilei
An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
title An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
title_full An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
title_fullStr An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
title_full_unstemmed An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
title_short An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
title_sort rna editing/dsrna binding-independent gene regulatory mechanism of adars and its clinical implication in cancer
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737565/
https://www.ncbi.nlm.nih.gov/pubmed/28985428
http://dx.doi.org/10.1093/nar/gkx667
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