Controlling Site‐Directed RNA Editing by Chemically Induced Dimerization

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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.
Funding Information
  • Deutsche Forschungsgemeinschaft (430214260, STA1053/7-1, STA1053/11-1)
  • H2020 European Research Council (CoG 647328)

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