- Project Identification
- Project Period
- 8/2015 - 7/2020
- Investor / Pogramme / Project type
- European Union
- MU Faculty or unit
- Central European Institute of Technology
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.
Total number of publications: 4