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RNActivate SIGNED

Optochemical control of cell fate by activation of mRNA translation

Total Cost €

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EC-Contrib. €

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Partnership

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 RNActivate project word cloud

Explore the words cloud of the RNActivate project. It provides you a very rough idea of what is the project "RNActivate" about.

biomolecular    single    methyltransferase    responsive    caged    ing    gene    genome    modification    synthetic    messenger    embryos    rna    abrogate    death    antisense    unmodified    photo    locally    cultured    lack    easily    transient    activate    overcome    cells    responsible    promiscuous    manipulate    canonical    organisms    tracking    conditional    triggered    external    transferring    eukaryotic    enabled    efficiency    turn    stage    cage    release    respective    temporal    producing    optochemical    block    light    uncompromised    translational    trigger    ectopic    migration    fate    form    biology    precision    remethylated    adenosylmethionine    labeling    translation    explore    prime    moieties    spatio    expression       organism    efficient    zebrafish    cellular    switch    molecular    exogenous    subpopulations    injected    adomet    groups    bulky    proteins    function    exploits    restore    cap    removal    small    wavelength    analogs    regulation    vivo    interfering    cell    excellent    capped    engineering    vital    cosubstrate    resolution    inducible    limitations    functions    agents    mrna    chemical    regulatory   

Project "RNActivate" data sheet

The following table provides information about the project.

Coordinator
WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER 

Organization address
address: SCHLOSSPLATZ 2
city: Munster
postcode: 48149
website: www.uni-muenster.de/en/

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˙990˙225 €
 EC max contribution 1˙990˙225 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-06-01   to  2023-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER DE (Munster) coordinator 1˙990˙225.00

Map

 Project objective

Light is an excellent external regulatory element that can be applied to cells and organisms with high spatio-temporal precision and without interfering with cellular processes. Optochemical biology exploits small photo-responsive chemical groups to cage and activate or to switch biomolecular functions in response to light of a defined wavelength. Caged antisense agents have enabled down-regulation of gene expression with spatio-temporal control at the messenger-RNA (mRNA) level in vivo, however approaches for triggering translation of exogenous mRNA lack efficient turn-on effects. To explore the effects of conditional and transient ectopic gene expression in a developing organism it is vital to fully abrogate and restore translational efficiency.

The goal of this project is to bring eukaryotic mRNA under the control of light to trigger efficient ectopic translation with spatio-temporal resolution in cells and in vivo. To achieve this, eukaryotic mRNA will be photo-caged at its 5′ cap using a highly promiscuous methyltransferase capable of transferring very bulky moieties from synthetic analogs of the cosubstrate S-adenosylmethionine (AdoMet). A single 5′ cap modification will block translation of the respective mRNA. Its light-triggered removal will release unmodified capped RNA, which in cells will be efficiently remethylated to form the canonical 5′ cap resulting in uncompromised translation.

In addition to labeling and tracking subpopulations of cells, we will use our technology to control and to manipulate cell fate by locally producing proteins responsible for cell death, genome engineering, and cell migration. We will use cultured cells and one-cell stage zebrafish embryos that can be easily injected with mRNA to study the function of ectopic gene expression in early development. Our approach will overcome current limitations of photo-inducible mRNA translation and enable us to manipulate a developing organism at the molecular level.

 Publications

year authors and title journal last update
List of publications.
2019 Lea Anhäuser, Nils Klöcker, Fabian Muttach, Florian Mäsing, Petr Špaček, Armido Studer, Andrea Rentmeister
A Benzophenone-Based Photocaging Strategy for the N7 Position of Guanosine
published pages: , ISSN: 1433-7851, DOI: 10.1002/anie.201914573
Angewandte Chemie International Edition 2020-02-04
2020 Nicolas V. Cornelissen, Freideriki Michailidou, Fabian Muttach, Kristina Rau, Andrea Rentmeister
Nucleoside-modified AdoMet analogues for differential methyltransferase targeting
published pages: , ISSN: 1359-7345, DOI: 10.1039/c9cc07807j
Chemical Communications 2020-01-29

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