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Controlling Site-Directed RNA Editing by Chemically Induced Dimerization.

ABSTRACT: 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.

SUBMITTER: Stroppel AS

PROVIDER: S-EPMC8456898 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Controlling Site-Directed RNA Editing by Chemically Induced Dimerization.

Stroppel Anna S AS Lappalainen Ruth R Stafforst Thorsten T

Chemistry (Weinheim an der Bergstrasse, Germany) 20210726 48

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 GAPD ...[more]

PMID: 34169589

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