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EXORICO SIGNED

Exosome and ribosome coupling

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 EXORICO project word cloud

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

assemblies    electron    principles    mediate    mechanisms    largely    mrnas    structures    molecular    metabolism    turnover    cerevisiae    opposite    execute    underpin    independently    reconstitutions    protein    unknown    degrade    isolate    individual    synthesize    cofactors    yeast    reveal    data    maturation    endogenous    crystallography    building    mrna    machines    destructive    gene    group    eukaryotic    proteins    combined    coupled    mda    bound    understand    microscopy    coordinate    biochemical    elimination    cryo    function    ribosome    ray    mechanistic    catalyze    structural    basis    macromolecular    complexes    rnas    degradation    combination    stalled    manner    multiprotein    cytoplasmic    visualize    suggests    date    80s    exosome    nuclear    deciphering    subunit    vitro    60s    individually    rna    preliminary    human    outcomes    ribosomal    genetic    coordinated    synthesis    expression    constructive    reactions    machine       interact    purifications    vivo   

Project "EXORICO" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

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 Germany [DE]
 Total cost 2˙004˙375 €
 EC max contribution 2˙004˙375 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 2˙004˙375.00

Map

 Project objective

To date, mechanistic studies on the macromolecular complexes that synthesize or degrade RNAs or proteins have investigated these machines individually to understand how they execute different steps in the gene expression process. Although the individual complexes catalyze their reactions independently of each other in vitro, increasing evidence suggests that they function in a highly coordinated manner in vivo. The molecular basis for such a coordination remains largely unknown. During the past five years, our group has focused on deciphering the mechanisms of multiprotein complexes that mediate mRNA turnover in S. cerevisiae. Here, I propose to take these analyses to the next level and visualize how a major RNA degradation machine, the exosome, is directly coupled to the protein-synthesis machine, the ribosome. In particular, we want to study two different exosome-ribosome assemblies that underpin opposite outcomes of RNA degradation: a constructive function of the nuclear exosome in the maturation of the large ribosomal subunit and a destructive function of the cytoplasmic exosome in the elimination of ribosome-bound mRNAs. Building on our preliminary data from both the yeast and human systems, we will use a combination of bottom-up biochemical reconstitutions and top-down endogenous purifications to isolate 1) an exosome complex and its nuclear cofactors bound to a pre-60S ribosomal subunit and 2) an exosome complex and its cytoplasmic cofactors bound to a stalled 80S ribosome. We will determine the structures of these ~3 - 4 MDa nuclear and cytoplasmic assemblies using the combined information from cryo-electron microscopy and X-ray crystallography approaches. The structural studies, combined with biochemical and genetic information, will reveal how these machines interact and coordinate RNA metabolism with protein synthesis. Overall, this work will provide important insight into the principles that coordinate different steps of eukaryotic gene expression.

 Publications

year authors and title journal last update
List of publications.
2018 Jan Michael Schuller, Sebastian Falk, Lisa Fromm, Ed Hurt, Elena Conti
Structure of the nuclear exosome captured on a maturing preribosome
published pages: 219-222, ISSN: 0036-8075, DOI: 10.1126/science.aar5428
Science 360/6385 2019-06-11
2018 Piotr Gerlach, Jan M Schuller, Fabien Bonneau, Jérôme Basquin, Peter Reichelt, Sebastian Falk, Elena Conti
Distinct and evolutionary conserved structural features of the human nuclear exosome complex
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.38686
eLife 7 2019-06-11

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