Objective
Pre-mRNA splicing is a fundamental maturation step of eukaryotic mRNAs that consists of the removal of introns and the concomitant ligation of exons by two successive transesterification reactions. This complex biological process is catalyzed by the spliceosome, a gigantic ribonucleoprotein particle that assembles de novo on each intron and uses a single RNA-based active site to perform both reactions.
The spliceosome is composed of five snRNPs (U1, U2, U4, U5, U6) that are recruited to pre-mRNAs in a stepwise manner. When a pre-catalytic spliceosome, consisting of all five snRNPs, is formed on a pre-mRNA it has no pre-existing active site and undergoes extensive compositional and conformational changes to become “catalytically competent”. During this transition, two snRNPs (U1 and U4) are lost and several new factors are recruited, ensuring the formation and stabilization of the active site as well as the correct positioning of the pre-mRNA’s reactive groups in the catalytic centre.
Thanks to recent technological advances in Electron Microscopy (EM), a series of cryoEM structures of fully assembled “active” spliceosomes at atomic resolution have been solved in the host group and elsewhere, in the past two years. These structures, which have created much excitement in the RNA community, visualize the spliceosome during each step of the catalytic cycle and allow a mechanistic understanding of catalysis. However, due to the scarcity of high-resolution information on earlier complexes, many questions remain regarding spliceosome activation.
My project aims at filling a gap in our understanding of pre-mRNA splicing by unraveling the molecular details of spliceosome activation. To that end, I will use a combination of biochemical characterization and cryoEM to study yeast spliceosome captured at discrete early stages of activation.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences chemical sciences catalysis
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2017
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
SN2 1FL SWINDON
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.