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TCAPS SIGNED

mRNA cap regulation and function in CD8 T cells

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EC-Contrib. €

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Project "TCAPS" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF DUNDEE 

Organization address
address: Nethergate
city: DUNDEE
postcode: DD1 4HN
website: www.dundee.ac.uk

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

 Coordinator Country United Kingdom [UK]
 Project website https://www.lifesci.dundee.ac.uk/people/victoria-cowling
 Total cost 1˙991˙387 €
 EC max contribution 1˙991˙387 € (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 2018-05-01   to  2023-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF DUNDEE UK (DUNDEE) coordinator 1˙991˙387.00

Map

 Project objective

CD8 T cells are vital for our response to infection, directly killing infected cells and stimulating other cells of the immune system. Major health problems world-wide involve deregulated T cells, including lymphomas, leukaemias, auto-immune disorders and organ transplant rejection. Damaging deficiencies of T cells are found in old-age. T cell development and response to pathogens is driven by regulated transcription and translation, however the mechanisms orchestrating this gene regulation are largely unknown, and are likely provide novel opportunities for therapeutic intervention. Our preliminary data reveals that a potent structure in gene expression, the mRNA cap, which co-ordinates RNA processing and translation initiation, is crucial for the development and activation of CD8 T cells. Regulation of mRNA cap formation is a novel concept in gene regulation in T cells, and also has not been studied in vivo previously. Our findings suggest the existence of an mRNA cap code, in which the different mRNA cap methylations regulate different genes and cellular functions. In TCAPS we will reveal how the mRNA cap code orchestrates CD8 T function. We will determine how the mRNA cap structures are regulated during CD8 T cell differentiation using the latest mass spectrometry technologies. We will determine the role of each mRNA cap methyltransferase in CD8 T cell gene expression during differentiation, using conditional knock-out mice in conjunction with enzyme biochemistry, RNA sequencing and quantitative mass spectrometry. We will determine the biological function of the mRNA cap methyltransferases in CD8 T cell survival and activation using immunological assays. TCAPS will also provide the first insight into the role of the mRNA cap code in vivo. The mRNA cap code is likely to be operational throughout mammalian physiology and therefore TCAPS will contribute significantly to our understanding of regulated gene expression in mammals.

 Publications

year authors and title journal last update
List of publications.
2019 Alison Galloway, Victoria H. Cowling
mRNA cap regulation in mammalian cell function and fate
published pages: 270-279, ISSN: 1874-9399, DOI: 10.1016/j.bbagrm.2018.09.011
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1862/3 2019-11-14
2019 Juan A Bueren-Calabuig, Marcus G. Bage, Victoria H Cowling, Andrei V Pisliakov
Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations
published pages: 8675–8692, ISSN: 0305-1048, DOI: 10.1093/nar/gkz613
Nucleic Acids Research 47 (16) 2019-11-14
2019 Victoria H. Cowling
CAPAM: The mRNA Cap Adenosine N6-Methyltransferase
published pages: 183-185, ISSN: 0968-0004, DOI: 10.1016/j.tibs.2019.01.002
Trends in Biochemical Sciences 44/3 2019-11-14

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