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MARS

Can histone code-like switches govern the multifunctionality of RNA-binding proteins?

Total Cost €

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EC-Contrib. €

0

Partnership

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 MARS project word cloud

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

wrong    status    inflammatory    gene    binding    ptm    understand    conferred    histone    multifunctional    modification    gap    1000    delineating    translation    bps    utilisation    disorders    diverse    hypothesis    paradigm    switches    quality    shared    residue    bind    methylation    networks    pabc    protein    pivotal    specificity    phenotypes    gametogenesis    deficiency    rna    ptms    mrnas    acetylations    multifunctionality    dimethylation    mrna    acetylation    impacts    functionally    proteins    domain    coordinate    regulated    consequently    operate    k606    interactions    unclear    coordinated    pabps    stability    memory    post    interacting    proteomic    motif    methylations    mechanistic    pabp    gt    pam2    regulators    aetiology    metabolism    manipulated    poly    neoplastic    physiological    expression    bases    dysregulation    site    multiple    transcriptional    human    regulation    uncovering    determines    fate    functions    regulatory    translational    central    learning    code    neurological    molecular    circuitry    highlighting   

Project "MARS" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF EDINBURGH 

Organization address
address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL
website: www.ed.ac.uk

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 United Kingdom [UK]
 Project website https://www.ed.ac.uk/centre-reproductive-health/professor-nicola-gray
 Total cost 183˙454 €
 EC max contribution 183˙454 € (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-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2019-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) coordinator 183˙454.00

Map

 Project objective

Post-transcriptional control of human gene expression is conferred by >1000 mRNA-binding proteins (RNA-BPs), which determine the utilisation and fate of mRNAs, with the aetiology of a wide-range of disorders (e.g. neurological, inflammatory, and neoplastic) being due to their dysregulation. Multifunctionality is a feature of RNA-BPs and understanding how this is coordinated and regulated is pivotal to delineating the molecular circuitry of post-transcriptional gene regulatory networks, to understand why they go wrong and how they may be manipulated. Poly(A)-binding proteins (PABPs) are central multifunctional regulators of mRNA fate, controlling multiple aspects of mRNA translation, stability and quality via interacting with functionally diverse protein partners. Consequently, their deficiency impacts physiological processes such as gametogenesis, metabolism and learning/memory, although mechanistic bases of these phenotypes are unclear, highlighting the importance of understanding their functions and regulation. A key gap in our knowledge is how PABP protein interactions, and therefore functions, are coordinated since many of its partners bind the same “PABC domain” site, through a shared “PAM2” motif. However, our recent findings lead to a novel hypothesis, which I will address, namely that the post-translational modification (PTM) status (acetylation or dimethylation) of a functionally important PABC residue, K606, determines PAM2-partner binding specificity and PABP multifunctionality. Uncovering that “histone-code like” acetylation-methylation switches operate in RNA-BPs, to coordinate their functions and achieve post-transcriptional regulation of mRNA networks, would represent a step-change in the state-of-the-art. This is especially timely since acetylations/methylations are emerging from proteomic studies as common in RNA-BPs and thus, PABP may provide an important paradigm for understanding how these PTMs coordinate post-transcriptional control.

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