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RNAEDIT SIGNED

RNA EDITING IN HEALTH AND DISEASE

Total Cost €

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EC-Contrib. €

0

Partnership

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 RNAEDIT project word cloud

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

testicular    proteomic    survival    heterogeneous    subtle    cytosine    contribution    either    prone    rna    stealthy    inosine    samples    human    sequence    edited    leads    disease    deciphered    programmed    mouse    tumour    output    fluctuations    subset    models    classes    min    cells    requirement    catalyzed    first    deaminases    macrophages    carcinomas    cellular    deficiency    additional    adenosine    immune    data    functionally    alterations    populations    diversifier    cancer    cell    previously    convert    hypothesize    instance    plasticity    generation    reduces    uracil    contexts    intestine    model    demonstrated    drives    context    significantly    single    mutation    hammarstrom    onslaught    select    fate    transcriptomes    protein    rapid    shown    apc    diverse    function    alteration    content    outcomes    plastic    genetic    editing    tumours    transcriptome    environmental    progression    population    transcripts    qp    adars    ki    settings    drive    stem    apobec1    burden    adenocarcinomas    extend    colon    understand   

Project "RNAEDIT" data sheet

The following table provides information about the project.

Coordinator
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG 

Organization address
address: IM NEUENHEIMER FELD 280
city: HEIDELBERG
postcode: 69120
website: www.dkfz.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 2˙270˙000 €
 EC max contribution 2˙270˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG DE (HEIDELBERG) coordinator 1˙839˙172.00
2    KAROLINSKA INSTITUTET SE (STOCKHOLM) participant 430˙827.00
3    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) participant 0.00

Map

 Project objective

'RNA editing is a type of programmed RNA sequence alteration that can result in a range of proteomic changes, from subtle fluctuations in output, to specific alterations in protein content. Editing is catalyzed by two classes of deaminases: those which convert adenosine to inosine (ADARs) and those which convert cytosine to uracil (APOBEC1). We have previously shown that APOBEC1-catalyzed editing in the transcriptome of macrophages leads to the generation of populations that are heterogeneous, and functionally diverse, enabling rapid population adaptation to different environmental settings.

Our first aim for this proposal is to extend our studies to additional immune cell subsets, focusing on cells that are recently recognized as 'plastic' to define the contribution of editing to this plasticity of fate and function.

RNA editing of the type we study has also been demonstrated to be crucial for cancer progression. For instance, APOBEC1-deficiency significantly reduces tumour burden on cells of the intestine and colon that are prone to adenocarcinomas in the context of the APC-min mutation. This is also the case for testicular carcinomas in mouse models of such tumours. Thus, there is genetic evidence for a requirement for APOBEC1 and RNA editing to drive tumour progression, in two tumour contexts. Based on these data and on our recently deciphered role for APOBEC1 as a 'stealthy' diversifier of cellular transcriptomes (and proteomic outcomes), we hypothesize that APOBEC1 drives tumour progression by editing select transcripts in tumour cells (or tumour stem cells), thus enabling the rapid adaptation of the tumour to the onslaught of the immune response.

Our second aim is to characterize the subset of edited transcripts in these model tumours (either at the population or at the single cell level) and understand their role to tumour survival and progression, both in mouse models of disease, and in human tumour samples (in collaboration with QP Hammarstrom, KI).'

 Publications

year authors and title journal last update
List of publications.
2017 Violeta Rayon-Estrada, Dewi Harjanto, Claire E. Hamilton, Yamina A. Berchiche, Emily Conn Gantman, Thomas P. Sakmar, Karen Bulloch, Khatuna Gagnidze, Sheila Harroch, Bruce S. McEwen, F. Nina Papavasiliou
Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function
published pages: 13296-13301, ISSN: 0027-8424, DOI: 10.1073/pnas.1714227114
Proceedings of the National Academy of Sciences 114/50 2019-06-07
2017 Daniel C. Cole, Youngcheul Chung, Khatuna Gagnidze, Kaitlyn H. Hajdarovic, Violeta Rayon-Estrada, Dewi Harjanto, Benedetta Bigio, Judit Gal-Toth, Teresa A. Milner, Bruce S. McEwen, F. Nina Papavasiliou, Karen Bulloch
Loss of APOBEC1 RNA-editing function in microglia exacerbates age-related CNS pathophysiology
published pages: 13272-13277, ISSN: 0027-8424, DOI: 10.1073/pnas.1710493114
Proceedings of the National Academy of Sciences 114/50 2019-06-07
2018 Khatuna Gagnidze, Violeta Rayon-Estrada, Sheila Harroch, Karen Bulloch, F. Nina Papavasiliou
A New Chapter in Genetic Medicine: RNA Editing and its Role in Disease Pathogenesis
published pages: 294-303, ISSN: 1471-4914, DOI: 10.1016/j.molmed.2018.01.002
Trends in Molecular Medicine 24/3 2019-06-07
2019 Taga Lerner, F. Papavasiliou, Riccardo Pecori
RNA Editors, Cofactors, and mRNA Targets: An Overview of the C-to-U RNA Editing Machinery and Its Implication in Human Disease
published pages: 13, ISSN: 2073-4425, DOI: 10.3390/genes10010013
Genes 10/1 2019-08-30
2019 Mitchell Kluesner, Annette Arnold, Taga Lerner, Rafail Nikolaos Tasakis, Sandra Wüst, Marco Binder, Branden S. Moriarity, Riccardo Pecori
MultiEditR: An easy validation method for detecting and quantifying RNA editing from Sanger sequencing
published pages: , ISSN: , DOI: 10.1101/633685
BioarXiv 2019-08-30

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