Project information
DECOR
(DECOR)
- Project Identification
- 649030
- Project Period
- 8/2015 - 7/2020
- Investor / Pogramme / Project type
-
European Union
- Horizon 2020
- ERC (Excellent Science)
- MU Faculty or unit
-
Central European Institute of Technology
- prof. Mgr. Richard Štefl, Ph.D.
- Mgr. Jaroslava Brůchová
I propose to decipher the basic rules that govern the readout of the CTD code of RNA polymerase II by RNA processing factors. The concept of the CTD code that specifies the position of RNA polymerase II in the transcriptional cycle and thus recruits specific processing factors, was suggested almost a decade ago. However, how the C-terminal domain (CTD) of RNA polymerase II recruits, activates, and displaces appropriate processing factors in coordination with the transcription cycle, remains obscure. Understanding the structural basis of the CTD code has been hindered by a lack of structural data and the players involved in the process.
In this project, we will determine 3D structures of several protein factors bound to the modified CTD, and establish structural and mechanistic basis of proline isomerisation in the CTD that control the timing of isomer specific protein-protein interactions. Furthermore, we will reveal how the overall CTD structure is remodelled by binding of multiple copies of processing factors and how these factors cross-talk and exchange with each other during the transcriptional cycle. To be able to address these important questions, we will combine small-angle scattering techniques with a high resolution NMR, and single molecule techniques. This combined approach will provide us with the entirely new structural information that will go significantly beyond the-state-of-the-art in the research fields of transcription and RNA processing. Furthermore, since a number of genetic disorders or human diseases (including cancer or neurodegenerative diseases) relate to abnormalities in RNA processing and proper ribonucleoprotein assembly, we anticipate that the detailed knowledge of mechanisms regulating the co-transcriptional processing will be of clinical value in the long term.
Publications
Total number of publications: 9
2023
-
Human senataxin is a bona fide R-loop resolving enzyme and transcription termination factor
Nucleic Acids Research, year: 2023, volume: 51, edition: 6, DOI
-
The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks
Cell Reports, year: 2023, volume: 42, edition: 12, DOI
2022
-
Cooperation between intrinsically disordered and ordered regions of Spt6 regulates nucleosome and Pol II CTD binding, and nucleosome assembly
Nucleic acids research, year: 2022, volume: 50, edition: 10, DOI
-
Structural and functional basis of mammalian microRNA biogenesis by Dicer
Molecular Cell, year: 2022, volume: 82, edition: 21, DOI
2021
-
PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC
Nature Communications, year: 2021, volume: 12, edition: 1, DOI
2020
-
Termination of non-coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD-mimicking region in Sen1
EMBO Journal, year: 2020, volume: 39, edition: 7, DOI
-
Yeast Spt6 Reads Multiple Phosphorylation Patterns of RNA Polymerase II C-Terminal Domain In Vitro
Journal of Molecular Biology, year: 2020, volume: 432, edition: 14, DOI
2019
-
Efficient and robust preparation of tyrosine phosphorylated intrinsically disordered proteins
BioTechniques, year: 2019, volume: 67, edition: 1, DOI
2017
-
Structure and dynamics of the RNAPII CTDsome with Rtt103
Proceeding of the National Academy of Sciences of the USA, year: 2017, volume: 114, edition: 42, DOI