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

Karthika Devi Kiran Kumar, Shubhangi Singh, Stella Maria Schmelzle, Paul Vogel, Carolin Fruhner, Alfred Hanswillemenke, Adrian Brun, Jacqueline Wettengel, Yvonne Füll, Lukas Funk, Valentin Mast, J. Josephine Botsch, Philipp Reautschnig, Jin Billy Li and Thorsten Stafforst ()
Additional contact information
Karthika Devi Kiran Kumar: University of Tübingen
Shubhangi Singh: University of Tübingen
Stella Maria Schmelzle: University of Tübingen
Paul Vogel: Stanford University
Carolin Fruhner: University of Tübingen
Alfred Hanswillemenke: University of Tübingen
Adrian Brun: University of Tübingen
Jacqueline Wettengel: University of Tübingen
Yvonne Füll: University of Tübingen
Lukas Funk: University of Tübingen
Valentin Mast: University of Tübingen
J. Josephine Botsch: University of Tübingen
Philipp Reautschnig: University of Tübingen
Jin Billy Li: Stanford University
Thorsten Stafforst: University of Tübingen

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50395-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50395-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50395-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().