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Structure-function studies of the general transcription factor IIIC (TFIIIC)

Objective

Transfer RNAs (tRNAs) act as adaptor molecules, decoding messenger RNA and delivering the correct amino acid to the growing peptide chain. Being instrumental in the cellular translation machinery, it is important to understand their synthesis mechanism. In eukaryotes, tRNA gene (tDNA) transcription begins with transcription factor IIIC (TFIIIC) bound to 2 gene-internal promoter elements, A- and B-box. This is followed by the recruitment of transcription factor IIIB and RNA polymerase III to form the transcription pre-initiation complex.
In ‘TF3C_EM’, I will focus on the mechanism and molecular architecture of the very first step, i.e. TFIIIC binding to tDNA. TFIIIC is composed of two subcomplexes, τA and τB, that bind respectively to the A- and B-box, and are flexibly linked to accommodate varying lengths between their binding sites. Interestingly, TFIIIC has recently been termed as ‘guardian of the genome’ in light of its extra transcriptional roles, such as chromatin remodelling. This further highlights the importance of exploring its underlying structure.
Using recombinantly purified TFIIIC, I will characterise the fully assembled TFIIIC complex and TFIIIC-tDNA interactions in vitro. To this end, an inter-disciplinary approach will be used, spanning complementing biophysical and structural techniques of single molecule FRET, cryo electron microscopy and X-ray crystallography.
Thus, in my project ‘TF3C_EM’, I will tackle 3 major objectives: (1) characterisation of the molecular architecture of TFIIIC, (2) understanding the tDNA recognition mechanism by TFIIIC and (3) understanding the dynamics between τA and τB. It will unravel the structure-function correlation of TFIIIC and pave the way for further understanding the transcription initiation by Pol III. At the same time, it will allow me to pursue research in an unparalleled scientific environment and significantly contribute to shape my future career as an independent researcher.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2015

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Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution

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.

€ 159 460,80
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost

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.

€ 159 460,80
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