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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.

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

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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