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

Projektinformationen

TF3C_EM

ID Finanzhilfevereinbarung: 703432

DOI 10.3030/703432

Das Projekt endete am 31 August 2018

EK-Unterschriftsdatum 31 März 2016

Startdatum 1 März 2017

Enddatum 28 Februar 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten € 159 460,80

EU-Beitrag € 159 460,80

Koordiniert durch

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany

Ziel

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.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › genetics › DNA
• natural sciences › earth and related environmental sciences › geology › mineralogy › crystallography
• natural sciences › physical sciences › optics › microscopy › electron microscopy
• natural sciences › biological sciences › genetics › RNA
• natural sciences › chemical sciences › organic chemistry › amines

Schlüsselbegriffe

• Transcription
• TFIIIC
• tRNA genes
• cryo-EM

Programm/Programme

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Thema/Themen

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)

Aufforderung zur Vorschlagseinreichung

H2020-MSCA-IF-2015

Finanzierungsplan

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

Koordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY

• Netto-EU-Beitrag: € 159 460,80
• Adresse: Meyerhofstrasse 1 ; 69117 Heidelberg ; Deutschland
• Region: Baden-Württemberg › Karlsruhe › Heidelberg, Stadtkreis
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 159 460,80