Objective
In higher eukaryotes, the RNA polymerase III (Pol III) participates in the transcription of small RNAs such as the tRNAs. RNA polymerase recruitment to their specific promoter relies on the activity of several transcription factors. Brf2 is a transcription factor that exclusively recruits RNA Pol III at the selenocysteine tRNA (tRNASec). Unpublished work from our group has unravelled an unanticipated central role of Brf2 in the oxidative stress response pathway, by acting as a cellular blockade during prolonged oxidative stress.
We are interested in understanding the molecular determinants that govern RNA Pol III recruitment at tRNASec promoter and its interaction with Brf2-bound promoters. In general, RNA Pol III subunit’s size is conserved amongst the eukaryotic kingdom. However, an exception is the human Rpc5 subunit, whose C terminus has 450 residues that are not present in its yeast counterpart C37. Similarly to Brf2, the Rpc5 C-terminal extension is only present in higher metazoans, which suggests a phylogenetic link between these two proteins. The recruiting mechanism of RNA Pol III to Brf2-dependent promoters has not been described to date. Preliminary results in our lab provide evidences that indeed Rpc5 C terminus is responsible for the accurate recruitment of RNA Pol III at TBP/Brf2/DNA complex. Interestingly, structural homology predictions indicated that the human Rpc5 C-terminal extension is a eukaryotic homologue of the prokaryotic protein SelB, a factor that interacts with the tRNASec and with a specific region of mRNAs, the SECIS-element, during translation of SeCys containing proteins. This similarity suggests a regulatory role for Rpc5 C terminus in the interaction with the SECIS-element and/or the tRNASec.
Our main objectives are to determine the structure of the Rpc5 C terminus in isolation and in complex with Brf2/TBP/DNA by X-ray crystallography and to characterise the role of Rpc5 C terminus in the context of tRNASec transcription.
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 genetics DNA
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-EF-ST - Standard EF
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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-2014
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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.
SW7 3RP London
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.