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Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization

Various RNA‐targeting approaches have been engineered to modify specific sites on endogenous transcripts, breaking new ground for a variety of basic research tools and promising clinical applications in the future. Here, we combine site‐directed adenosine‐to‐inosine RNA editing with chemically induc...

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Detalles Bibliográficos
Autores principales: Stroppel, Anna S., Lappalainen, Ruth, Stafforst, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456898/
https://www.ncbi.nlm.nih.gov/pubmed/34169589
http://dx.doi.org/10.1002/chem.202101985
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author Stroppel, Anna S.
Lappalainen, Ruth
Stafforst, Thorsten
author_facet Stroppel, Anna S.
Lappalainen, Ruth
Stafforst, Thorsten
author_sort Stroppel, Anna S.
collection PubMed
description Various RNA‐targeting approaches have been engineered to modify specific sites on endogenous transcripts, breaking new ground for a variety of basic research tools and promising clinical applications in the future. Here, we combine site‐directed adenosine‐to‐inosine RNA editing with chemically induced dimerization. Specifically, we achieve tight and dose‐dependent control of the editing reaction with gibberellic acid, and obtain editing yields up to 20 % and 44 % in the endogenous STAT1 and GAPDH transcript in cell culture. Furthermore, the disease‐relevant MECP2 R106Q mutation was repaired with editing yields up to 42 %. The introduced principle will enable new applications where temporal or spatiotemporal control of an RNA‐targeting mechanism is desired.
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spelling pubmed-84568982021-09-27 Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization Stroppel, Anna S. Lappalainen, Ruth Stafforst, Thorsten Chemistry Communications Various RNA‐targeting approaches have been engineered to modify specific sites on endogenous transcripts, breaking new ground for a variety of basic research tools and promising clinical applications in the future. Here, we combine site‐directed adenosine‐to‐inosine RNA editing with chemically induced dimerization. Specifically, we achieve tight and dose‐dependent control of the editing reaction with gibberellic acid, and obtain editing yields up to 20 % and 44 % in the endogenous STAT1 and GAPDH transcript in cell culture. Furthermore, the disease‐relevant MECP2 R106Q mutation was repaired with editing yields up to 42 %. The introduced principle will enable new applications where temporal or spatiotemporal control of an RNA‐targeting mechanism is desired. John Wiley and Sons Inc. 2021-07-26 2021-08-25 /pmc/articles/PMC8456898/ /pubmed/34169589 http://dx.doi.org/10.1002/chem.202101985 Text en © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Communications
Stroppel, Anna S.
Lappalainen, Ruth
Stafforst, Thorsten
Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization
title Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization
title_full Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization
title_fullStr Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization
title_full_unstemmed Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization
title_short Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization
title_sort controlling site‐directed rna editing by chemically induced dimerization
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456898/
https://www.ncbi.nlm.nih.gov/pubmed/34169589
http://dx.doi.org/10.1002/chem.202101985
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