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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.

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

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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