EU H2020 Project "TF3C_EM (Structure-function studies of the general transcription factor IIIC (TFIIIC))": description, partecipants, costs and EC-fundings

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TF3C_EM project word cloud

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researcher sites tau respectively scientific adaptor subcomplexes lengths shape begins biophysical pave function remodelling correlation gene me termed guardian chromatin box cryo rnas characterise tf3c machinery correct significantly techniques structure recruitment acid exploring vitro inter roles em binding environment spanning genome synthesis crystallography microscopy interestingly promoter messenger internal purified unravel chain interactions trna electron highlights career eukaryotes bound independent underlying cellular extra tfiiic amino delivering ray rna iiic varying first assembled decoding light linked molecule form transcription bind disciplinary architecture molecules polymerase time single recognition dynamics complementing recombinantly followed initiation pol accommodate translation trnas act transfer molecular unparalleled peptide pursue fret iiib tdna characterisation mechanism flexibly transcriptional structural understand instrumental tackle

Project "TF3C_EM" data sheet

The following table provides information about the project.

Coordinator	EUROPEAN MOLECULAR BIOLOGY LABORATORY Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 website: http://www.embl.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Germany [DE]
Total cost	159˙460 €
EC max contribution	159˙460 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2015
Funding Scheme	MSCA-IF-EF-ST
Starting year	2017
Duration (year-month-day)	from 2017-03-01 to 2019-02-28

#	participants	country	role	EC contrib. [€]
1	EUROPEAN MOLECULAR BIOLOGY LABORATORY	DE (HEIDELBERG)	coordinator	159˙460.00

EUROPEAN MOLECULAR BIOLOGY LABORATORY

DE (HEIDELBERG)

coordinator

159˙460.00

Project 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.

Publications

List of publications.
year	authors and title	journal	last update
2017	Heena Khatter, Matthias K VorlÃ¤nder, Christoph W MÃ¼ller RNA polymerase I and III: similar yet unique published pages: 88-94, ISSN: 0959-440X, DOI: 10.1016/j.sbi.2017.05.008	Current Opinion in Structural Biology 47	2019-06-13
2018	Matthias K. VorlÃ¤nder, Heena Khatter, Rene Wetzel, Wim J. H. Hagen, Christoph W. MÃ¼ller Molecular mechanism of promoter opening by RNA polymerase III published pages: 295-300, ISSN: 0028-0836, DOI: 10.1038/nature25440	Nature 553/7688	2019-06-13

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