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SPLICE3D SIGNED

CryoEM studies of the spliceosome

Total Cost €

0

EC-Contrib. €

0

Partnership

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 SPLICE3D project word cloud

Explore the words cloud of the SPLICE3D project. It provides you a very rough idea of what is the project "SPLICE3D" about.

machine    building    mrna    excision    plays    therapeutic    site    u6    u5    compositional    eukaryotic    u2    u1    rna    intervention    nuclear    tri    spliceosomal    diseases    enormously    achievements    cryoem    components    harbours    complete    sequences    organisation    revealed    solved    proteins    assembled    reaction    expression    entire    extensive    branch    prp8    pathology    remodeling    snrna    crystal    rearrangement    stalled    activation    structure    splice    mrnas    snrnp    interrupted    structural    spliceosome    majority    point    mature    molecular    exons    snrnps    small    protein    activated    active    recruited    coding    bind    insights    determined    becomes    canonical    gene    catalyses    caused    catalytic    introns    initial    fundamental    particles    clarify    subunits    intricate    brr2    nearly    respectively    interaction    mutations    stages    leads    network    immense    core    mechanism    ribonucleoprotein    genes    splicing    u4   

Project "SPLICE3D" data sheet

The following table provides information about the project.

Coordinator
UNITED KINGDOM RESEARCH AND INNOVATION 

There are not information about this coordinator. Please contact Fabio for more information, thanks.

 Coordinator Country United Kingdom [UK]
 Project website https://www2.mrc-lmb.cam.ac.uk/groups/nagai/
 Total cost 1˙069˙584 €
 EC max contribution 1˙069˙584 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNITED KINGDOM RESEARCH AND INNOVATION UK (SWINDON) coordinator 1˙069˙584.00
2    MEDICAL RESEARCH COUNCIL UK (SWINDON) coordinator 0.00

Map

 Project objective

The protein coding sequences of the majority of eukaryotic genes are interrupted by non-coding introns. The spliceosome is an immense and intricate molecular machine that catalyses the excision of introns from pre-mRNAs and splicing together of exons to produce mature mRNA. This is a crucial process in eukaryotic gene expression and we aims to greatly increase our understanding of its molecular mechanism through cryoEM studies of the spliceosome. The spliceosome comprises five canonical subunits, namely U1, U2, U4, U5 and U6 small nuclear ribonucleoprotein particles (snRNPs) and numerous non-snRNP factors. During the initial stages, U1 and U2 snRNPs bind the 5’-splice site and branch point of pre-mRNA, respectively, and the spliceosome is fully assembled when the U4/U6.U5 tri-snRNP is recruited. The spliceosome then becomes activated through extensive structural and compositional remodeling which leads to the formation of the catalytic RNA core. Recently we determined the crystal structure of U1 snRNP and two key spliceosomal proteins: Prp8, which harbours the catalytic RNA core and Brr2, which catalyses the rearrangement of the RNA interaction network and plays a crucial role in spliceosomal activation. We also solved the structure of U4/U6.U5 tri-snRNP by cryoEM and revealed the nearly complete organisation of U5 snRNA and U4/U6 snRNA and over 30 proteins within this complex, providing crucial insights into the activation mechanism and the active site of the spliceosome. Building on these achievements we aim to determine the structure of the entire spliceosome stalled at different steps of the splicing reaction so that the molecular mechanism of pre-mRNA splicing is understood in structural terms. This will enormously increase our understanding of this fundamental process of eukaryotic gene expression and such knowledge will clarify the molecular pathology of diseases caused by mutations in spliceosomal components and may facilitate therapeutic intervention.

 Publications

year authors and title journal last update
List of publications.
2018 Clemens Plaschka, Pei-Chun Lin, Clément Charenton, Kiyoshi Nagai
Prespliceosome structure provides insights into spliceosome assembly and regulation
published pages: 419-422, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0323-8
Nature 559/7714 2020-01-15
2017 Sebastian M. Fica, Chris Oubridge, Wojciech P. Galej, Max E. Wilkinson, Xiao-Chen Bai, Andrew J. Newman, Kiyoshi Nagai
Structure of a spliceosome remodelled for exon ligation
published pages: 377-380, ISSN: 0028-0836, DOI: 10.1038/nature21078
Nature 542/7641 2020-01-15
2019 Clément Charenton, Max E. Wilkinson, Kiyoshi Nagai
Mechanism of 5′ splice site transfer for human spliceosome activation
published pages: eaax3289, ISSN: 0036-8075, DOI: 10.1126/science.aax3289
Science 2020-01-15
2019 Sebastian M. Fica, Chris Oubridge, Max E. Wilkinson, Andrew J. Newman, Kiyoshi Nagai
A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation
published pages: eaaw5569, ISSN: 0036-8075, DOI: 10.1126/science.aaw5569
Science 2020-01-15
2019 Clemens Plaschka, Andrew J. Newman, Kiyoshi Nagai
Structural Basis of Nuclear pre-mRNA Splicing: Lessons from Yeast
published pages: a032391, ISSN: 1943-0264, DOI: 10.1101/cshperspect.a032391
Cold Spring Harbor Perspectives in Biology 2020-01-15

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The information about "SPLICE3D" are provided by the European Opendata Portal: CORDIS opendata.

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