Project description
Mechanistic insight into the post-transcriptional control of RNA
Eukaryotic cells have evolved various mechanisms for ensuring the quality of their genetic information at all levels. The RNA exosome complex constitutes such a mechanism with a central role in several aspects of eukaryotic RNA biogenesis, including RNA maturation and surveillance. It is involved in RNA quality control in the nucleus and degrades aberrant RNA molecules that have not matured properly. The scope of the EU-funded EXOonRNA project is to understand how the RNA exosome identifies and eliminates non-functional RNAs. Researchers will undertake a multidisciplinary approach to delineate the underlying mechanisms and provide answers related to the timely function of this complex in RNA decay.
Objective
The human genome is ubiquitously transcribed into far more RNA than is immediately needed. Consequently, RNA turnover becomes critical for keeping our cells healthy. The nuclear RNA exosome degrades the majority of short-lived RNA species within cell nuclei and is hereby the gatekeeper of an enormous RNA synthesis output. To perform this essential task, the exosome employs so-called ‘adaptor complexes’ (ExoACs), which contribute to target specificity. While the trimeric nuclear exosome targeting (NEXT) complex is specifically required for the degradation of short RNA transcripts, the poly(A) tail exosome targeting (PAXT) connection recruits the exosome to longer polyadenylated RNAs. Interestingly, and in contrast to NEXT, PAXT exhibits a rather complex nature. Besides the integral component RNA helicase MTR4 and the large scaffolding protein ZFC3H1, the proteins PABPN1, ZC3H3, and RBM26/27 participate in the RNA-targeting of PAXT. How assembly of all these proteins is achieved to commit a polyadenylated RNA for decay and how it is balanced with other nuclear RNA metabolic processes to avoid untimely decay of mRNA is unknown.
Here, I will track the interaction of the RNA-binding components of NEXT and PAXT with newly synthesized RNA in human cells using a novel and cutting-edge temporally resolved CLIP (T-CLIP) methodology, which combines nascent RNA labeling using photoactivatable ribonucleoside analogue 4-thiouridine with the time course of UV crosslinking of protein-RNA complexes. Since the T-CLIP approach allows us to link ExoAC interaction profiles to RNA synthesis and turnover data, I will define the positioning and timing of ExoAC component interactions with nuclear RNA in real-time to understand how nuclear exosome identify and eliminate nonfunctional RNA. In achieving my aim, I will critically further our understanding of how the cells in our bodies manage to quality control their genetic information through the post-transcriptional control of RNA levels.
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 biological sciences biochemistry biomolecules proteins
- 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.
8000 Aarhus C
Denmark
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.