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IAV-m6A SIGNED

Elucidating the role of m6A RNA methylation on the replication and pathogenesis of influenza A virus.

Total Cost €

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EC-Contrib. €

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Partnership

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Project "IAV-m6A" data sheet

The following table provides information about the project.

Coordinator
INSTITUT PASTEUR 

Organization address
address: RUE DU DOCTEUR ROUX 25-28
city: PARIS CEDEX 15
postcode: 75724
website: http://www.pasteur.fr

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 France [FR]
 Project website http://www.davidgcourtney.com
 Total cost 264˙668 €
 EC max contribution 264˙668 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-GF
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT PASTEUR FR (PARIS CEDEX 15) coordinator 264˙668.00
2    DUKE UNIVERSITY US (DURHAM NC) partner 0.00

Map

 Project objective

It has recently become apparent that post-transcriptional editing of mRNA by methylation of adenosines (m6A) plays a key role in regulating gene expression. In particular, total loss of m6A editing blocks the development of early embryos in a number of organisms. However, how m6A modifications, which are added in the nucleus and primarily detected by 3 cytoplasmic “reader” proteins, exert their effects remains unknown. The presence of m6A on viral transcripts has been known for 40 years, yet has only recently been shown to enhance HIV-1 gene expression and replication. Influenza A virus (IAV) that, like HIV-1, replicates in the nucleus, is known to bear a high level of m6A on viral RNA. However, whether and how m6A editing affects IAV replication remains unknown. Here, the researcher proposes the investigation of the role of m6A in IAV pathogenesis. The main objectives of this proposal are; to compile a precise map of m6A sites on IAV-PR8 RNA, determine their functional significance on replication and RNA trafficking, assess how m6A machinery is altered in IAV infected cells, and evaluate the conservation of these sites across additional pathogenic IAV strains. Preliminary data demonstrates that IAV gene expression may be enhanced by overexpression of the m6A reader proteins. Therefore the researcher proposes that IAV may subvert the m6A modification pathway to enhance viral RNA expression. Mapping of m6A modifications will be performed using PAR-CLIP and PA-m6A-seq, while RNAi, CRISPR knockouts and lentiviral overexpression systems will be utilised to determine the functional role of m6A editing on IAV pathogenesis. This fellowship will provide the researcher with an excellent opportunity to work at 2 highly regarded research institutes and advance his knowledge in virology and RNA biology. The skills acquired through completion of this fellowship will greatly assist him in his future endeavours including the establishment of his own European research group.

 Publications

year authors and title journal last update
List of publications.
2019 David G. Courtney, Andrea Chalem, Hal P. Bogerd, Brittany A. Law, Edward M. Kennedy, Christopher L. Holley, Bryan R. Cullen
Extensive Epitranscriptomic Methylation of A and C Residues on Murine Leukemia Virus Transcripts Enhances Viral Gene Expression
published pages: , ISSN: 2150-7511, DOI: 10.1128/mbio.01209-19
mBio 10/3 2019-08-05
2017 David G. Courtney, Edward M. Kennedy, Rebekah E. Dumm, Hal P. Bogerd, Kevin Tsai, Nicholas S. Heaton, Bryan R. Cullen
Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication
published pages: 377-386.e5, ISSN: 1931-3128, DOI: 10.1016/j.chom.2017.08.004
Cell Host & Microbe 22/3 2019-06-11
2018 Kevin Tsai, David G. Courtney, Edward M. Kennedy, Bryan R. Cullen
Influenza A virus-derived siRNAs increase in the absence of NS1 yet fail to inhibit virus replication
published pages: rna.066332.118, ISSN: 1355-8382, DOI: 10.1261/rna.066332.118
RNA 2019-06-11
2018 Kevin Tsai, David G. Courtney, Bryan R. Cullen
Addition of m6A to SV40 late mRNAs enhances viral structural gene expression and replication
published pages: e1006919, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006919
PLOS Pathogens 14/2 2019-06-11

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