Project description
Visualising human mRNA export
Regulation of gene expression in eukaryotic cells occurs at various stages before, during and after transcription. Newly made messenger RNAs (mRNAs) must be selected and exported from the cell nucleus into the cytoplasm, where they are translated into proteins. The EU-funded TREXSpliceosome project focuses on the process of mRNA export from the nucleus and the mechanism by which the multi-subunit transcription and export (TREX) complex selects and escorts mRNA molecules. Given that TREX has been associated with various diseases, including cancer, the expected results have wider implications for genome stability.
Objective
Eukaryotic mRNA is transcribed, capped, spliced and poly-adenylated in the nucleus, but translated in the cytoplasm. Nuclear mRNA export is a key step in gene expression which is still poorly understood in mechanistic detail, but the multi-subunit transcription and export (TREX) complex plays a central role in the process. TREX bridges transcription, RNA processing and packaging to facilitate mRNA export licensing. Understanding TREX function is relevant to human health, as TREX protects against transcription-associated genome instability, is required for development, and has been linked to human disease, including several types of cancer. Despite its importance, many questions about TREX function remain, in particular, how is TREX recruited to mRNA and how is the export factor NXF1-NXT1 deposited on mature mRNA?
Here, I propose to study the mechanistic basis of TREX recruitment and function using structural biology and imaging approaches. The host laboratory recently purified an endogenous multi-megadalton spliceosome–TREX complex, whose three-dimensional cryo-EM structure I aim to determine. This will reveal how TREX is recruited to maturing mRNA to read out and relay the presence of activating and repressive marks to, ultimately, decide whether or not to export the mRNA. In close collaboration with the Balzarotti lab (IMP), I will use super-resolution microscopy (MINFLUX) to visualize post-recruitment functions of TREX in situ and test models of how deposition of the mRNA export factor NXF1-NXT is linked to export competence. Taken together, the proposed work will significantly enhance our understanding of TREX as a chaperone of nuclear mRNA processing and export.
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 super resolution microscopy
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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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-2020
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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.
1030 Wien
Austria
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.