An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification

RNA base editing relies on the introduction of adenosine-to-inosine changes into target RNAs in a highly programmable manner in order to repair disease-causing mutations. Here, we propose that RNA base editing could be broadly applied to perturb protein function by removal of regulatory phosphorylation and acetylation sites. We demonstrate the feasibility on more than 70 sites in various signaling proteins and identify key determinants for high editing efficiency and potent down-stream effects. For the JAK/STAT pathway, we demonstrate both, negative and positive regulation. To achieve high editing efficiency over a broad codon scope, we applied an improved version of the SNAP-ADAR tool. The transient nature of RNA base editing enables the comparably fast (hours to days), dose-dependent (thus partial) and reversible manipulation of regulatory sites, which is a key advantage over DNA (base) editing approaches. In summary, PTM interference might become a valuable field of application of RNA base editing.

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Publication Details

Journal
Nature Communications
Published
2024-08-05
DOI
https://doi.org/10.1038/s41467-024-50395-w
Citations
16
Primary Topic
RNA regulation and disease
Type
article
Field-Weighted Citation Impact
3.74

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article

An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification

L.-M. Funk, Yvonne Füll, Alfred Hanswillemenke, Paul Vogel et al.
16 citations
Nature Communications
RNA regulation and disease
3.74
article

An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification

L.-M. Funk, Yvonne Füll, Alfred Hanswillemenke, Paul Vogel, Thorsten Stafforst, J. Josephine Botsch, Jin Billy Li, Philipp Reautschnig, Jacqueline Wettengel, Carolin Fruhner, Stella Maria Schmelzle, Shubhangi Singh, Valentin Mast, Adrian Brun, Karthika Devi Kiran Kumar
article en
16 citations

Abstract

RNA base editing relies on the introduction of adenosine-to-inosine changes into target RNAs in a highly programmable manner in order to repair disease-causing mutations. Here, we propose that RNA base editing could be broadly applied to perturb protein function by removal of regulatory phosphorylation and acetylation sites. We demonstrate the feasibility on more than 70 sites in various signaling proteins and identify key determinants for high editing efficiency and potent down-stream effects. For the JAK/STAT pathway, we demonstrate both, negative and positive regulation. To achieve high editing efficiency over a broad codon scope, we applied an improved version of the SNAP-ADAR tool. The transient nature of RNA base editing enables the comparably fast (hours to days), dose-dependent (thus partial) and reversible manipulation of regulatory sites, which is a key advantage over DNA (base) editing approaches. In summary, PTM interference might become a valuable field of application of RNA base editing.

Nature CommunicationsVol. 15(1)
Bernstein Center for Computational Neuroscience Tübingen (DE), University of Tübingen (DE), Stanford University (US)
Deutsche Forschungsgemeinschaft, Volkswagen Foundation, Eberhard Karls Universität Tübingen, Deutsche Akademie der Naturforscher Leopoldina - Nationale Akademie der Wissenschaften
Openalex Percentile: Top 6%
RNA regulation and disease
3.74
DOIOpen Access PDFOpenAlex
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