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RNArepair SIGNED

Site-directed RNA Editing to Manipulate RNA and Protein Function

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EC-Contrib. €

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Project "RNArepair" data sheet

The following table provides information about the project.

Coordinator
EBERHARD KARLS UNIVERSITAET TUEBINGEN 

Organization address
address: GESCHWISTER-SCHOLL-PLATZ
city: TUEBINGEN
postcode: 72074
website: www.uni-tuebingen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙808˙200 €
 EC max contribution 1˙808˙200 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-08-01   to  2020-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EBERHARD KARLS UNIVERSITAET TUEBINGEN DE (TUEBINGEN) coordinator 1˙808˙200.00

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 Project objective

Enzymatically active RNA-guided proteins, like the RNA-induced silencing complex (RISC), are particularly versatile tools for the rationally programmed manipulation of genetic information. After successful re-addressing of various natural RNA-guided machineries it is now time to tackle the engineering of novel, user-defined tools. With this respect we have recently achieved the engineering of an RNA-guided adenosine-to-inosine RNA editing machinery. Since inosine is biochemically read as guanosine, A-to-I editing alters genomic information on the RNA-level and may potentially allow for the manipulation of RNA processing or protein function. We have already achieved to apply our RNA editing approach for the repair of several missense and nonsense point mutations on reporter and disease-related genes in vitro and demonstrated its applicability in mammalian cell culture.

Now, we want to push the method further towards application. To enable editing in oocytes, primary cells and neurons, we will establish to deliver the editing tool by lentiviral vectors and stabilized mRNAs. We further aim to create cell lines expressing the artificial editing machinery under conditional control. We will repair reporter genes in developing worm oocytes, and we want to reconstitute mutations that cause neuro-diseases. We also wish to establish new features including photocontrol and the application of editing to steer protein localization.

If successful, site-directed RNA editing will enable us to manipulate RNA and protein function in a yet unprecedented way. The ready introduction of point mutations into mRNAs without the need for genomic engineering may dramatically facilitate the study of protein function, disease mechanism and may even allow for the treatment of diseases based on personalized genetic information.

 Publications

year authors and title journal last update
List of publications.
2017 Paul Vogel, Alfred Hanswillemenke, Thorsten Stafforst
Switching Protein Localization by Site-Directed RNA Editing under Control of Light
published pages: 1642-1649, ISSN: 2161-5063, DOI: 10.1021/acssynbio.7b00113
ACS Synthetic Biology 6/9 2019-06-06
2016 Philipp Reautschnig, Paul Vogel, Thorsten Stafforst
The notorious R.N.A. in the spotlight - drug or target for the treatment of disease
published pages: 651-668, ISSN: 1547-6286, DOI: 10.1080/15476286.2016.1208323
RNA Biology 14/5 2019-06-06
2015 Alfred Hanswillemenke, Tahsin Kuzdere, Paul Vogel, Gáspár Jékely, Thorsten Stafforst
Site-Directed RNA Editing in Vivo Can Be Triggered by the Light-Driven Assembly of an Artificial Riboprotein
published pages: 15875-15881, ISSN: 0002-7863, DOI: 10.1021/jacs.5b10216
Journal of the American Chemical Society 137/50 2019-06-06

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