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

Información del proyecto

TF3C_EM

Identificador del acuerdo de subvención: 703432

DOI

10.3030/703432

Proyecto finalizado el 31 Agosto 2018

Fecha de la firma de la CE 31 Marzo 2016

Fecha de inicio 1 Marzo 2017

Fecha de finalización 28 Febrero 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 159 460,80

Aportación de la UE

€ 159 460,80

Coordinado por

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany

Objetivo

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.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › genética › ADN
• ciencias naturales › ciencias de la tierra y ciencias ambientales conexas › geología › mineralogía › cristalografía
• ciencias naturales › ciencias físicas › óptica › microscopía › electron microscopy
• ciencias naturales › ciencias biológicas › genética › ARN
• ciencias naturales › ciencias químicas › química orgánica › aminas

Palabras clave

• Transcription
• TFIIIC
• tRNA genes
• cryo-EM

Programa(s)

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

Tema(s)

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

Régimen de financiación

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

Convocatoria de propuestas

H2020-MSCA-IF-2015

Coordinador

EUROPEAN MOLECULAR BIOLOGY LABORATORY

• Aportación neta de la UEn: € 159 460,80
• Dirección: Meyerhofstrasse 1 ; 69117 Heidelberg ; Alemania
• Región: Baden-Württemberg › Karlsruhe › Heidelberg, Stadtkreis
• Tipo de actividad: Research Organisations
• Coste total: € 159 460,80