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MARS

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

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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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.

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

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

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 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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