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EXORICO SIGNED

Exosome and ribosome coupling

Total Cost €

0

EC-Contrib. €

0

Partnership

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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.

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

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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