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RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing

Adenosine-to-inosine RNA editing is catalyzed by nuclear adenosine deaminase acting on RNA 1 (ADAR1) p110 and ADAR2, and cytoplasmic ADAR1 p150 in mammals, all of which recognize dsRNAs as targets. RNA editing occurs in some coding regions, which alters protein functions by exchanging amino acid seq...

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Autores principales: Xing, Yanfang, Nakahama, Taisuke, Wu, Yuke, Inoue, Maal, Kim, Jung In, Todo, Hiroyuki, Shibuya, Toshiharu, Kato, Yuki, Kawahara, Yukio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404624/
https://www.ncbi.nlm.nih.gov/pubmed/37209819
http://dx.doi.org/10.1016/j.jbc.2023.104840
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author Xing, Yanfang
Nakahama, Taisuke
Wu, Yuke
Inoue, Maal
Kim, Jung In
Todo, Hiroyuki
Shibuya, Toshiharu
Kato, Yuki
Kawahara, Yukio
author_facet Xing, Yanfang
Nakahama, Taisuke
Wu, Yuke
Inoue, Maal
Kim, Jung In
Todo, Hiroyuki
Shibuya, Toshiharu
Kato, Yuki
Kawahara, Yukio
author_sort Xing, Yanfang
collection PubMed
description Adenosine-to-inosine RNA editing is catalyzed by nuclear adenosine deaminase acting on RNA 1 (ADAR1) p110 and ADAR2, and cytoplasmic ADAR1 p150 in mammals, all of which recognize dsRNAs as targets. RNA editing occurs in some coding regions, which alters protein functions by exchanging amino acid sequences, and is therefore physiologically significant. In general, such coding sites are edited by ADAR1 p110 and ADAR2 before splicing, given that the corresponding exon forms a dsRNA structure with an adjacent intron. We previously found that RNA editing at two coding sites of antizyme inhibitor 1 (AZIN1) is sustained in Adar1 p110/Aadr2 double KO mice. However, the molecular mechanisms underlying RNA editing of AZIN1 remain unknown. Here, we showed that Azin1 editing levels were increased upon type I interferon treatment, which activated Adar1 p150 transcription, in mouse Raw 264.7 cells. Azin1 RNA editing was observed in mature mRNA but not precursor mRNA. Furthermore, we revealed that the two coding sites were editable only by ADAR1 p150 in both mouse Raw 264.7 and human embryonic kidney 293T cells. This unique editing was achieved by forming a dsRNA structure with a downstream exon after splicing, and the intervening intron suppressed RNA editing. Therefore, deletion of a nuclear export signal from ADAR1 p150, shifting its localization to the nucleus, decreased Azin1 editing levels. Finally, we demonstrated that Azin1 RNA editing was completely absent in Adar1 p150 KO mice. Thus, these findings indicate that RNA editing of AZIN1 coding sites is exceptionally catalyzed by ADAR1 p150 after splicing.
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spelling pubmed-104046242023-08-08 RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing Xing, Yanfang Nakahama, Taisuke Wu, Yuke Inoue, Maal Kim, Jung In Todo, Hiroyuki Shibuya, Toshiharu Kato, Yuki Kawahara, Yukio J Biol Chem Research Article Adenosine-to-inosine RNA editing is catalyzed by nuclear adenosine deaminase acting on RNA 1 (ADAR1) p110 and ADAR2, and cytoplasmic ADAR1 p150 in mammals, all of which recognize dsRNAs as targets. RNA editing occurs in some coding regions, which alters protein functions by exchanging amino acid sequences, and is therefore physiologically significant. In general, such coding sites are edited by ADAR1 p110 and ADAR2 before splicing, given that the corresponding exon forms a dsRNA structure with an adjacent intron. We previously found that RNA editing at two coding sites of antizyme inhibitor 1 (AZIN1) is sustained in Adar1 p110/Aadr2 double KO mice. However, the molecular mechanisms underlying RNA editing of AZIN1 remain unknown. Here, we showed that Azin1 editing levels were increased upon type I interferon treatment, which activated Adar1 p150 transcription, in mouse Raw 264.7 cells. Azin1 RNA editing was observed in mature mRNA but not precursor mRNA. Furthermore, we revealed that the two coding sites were editable only by ADAR1 p150 in both mouse Raw 264.7 and human embryonic kidney 293T cells. This unique editing was achieved by forming a dsRNA structure with a downstream exon after splicing, and the intervening intron suppressed RNA editing. Therefore, deletion of a nuclear export signal from ADAR1 p150, shifting its localization to the nucleus, decreased Azin1 editing levels. Finally, we demonstrated that Azin1 RNA editing was completely absent in Adar1 p150 KO mice. Thus, these findings indicate that RNA editing of AZIN1 coding sites is exceptionally catalyzed by ADAR1 p150 after splicing. American Society for Biochemistry and Molecular Biology 2023-05-18 /pmc/articles/PMC10404624/ /pubmed/37209819 http://dx.doi.org/10.1016/j.jbc.2023.104840 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Xing, Yanfang
Nakahama, Taisuke
Wu, Yuke
Inoue, Maal
Kim, Jung In
Todo, Hiroyuki
Shibuya, Toshiharu
Kato, Yuki
Kawahara, Yukio
RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
title RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
title_full RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
title_fullStr RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
title_full_unstemmed RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
title_short RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
title_sort rna editing of azin1 coding sites is catalyzed by adar1 p150 after splicing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404624/
https://www.ncbi.nlm.nih.gov/pubmed/37209819
http://dx.doi.org/10.1016/j.jbc.2023.104840
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