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Control of RNA Polymerase II and Transcription Factors via IDRs

Objective

RNA Polymerase II (Pol II) plays a pivotal role in human cellular function, carrying out the complex transcription process. A unique domain sits at the end of Pol II, the C-Terminal Domain (CTD), the phosphorylation of which offers a mechanism of interaction for transcription factors (TFs) that regulate the transcription process. The spatial organization of TFs around Pol II is moderated by the intrinsically disordered regions (IDRs) of the TFs and CTD, and high specificity is required to avoid disease causing defects. However, the exact mechanisms that maintain this environment, and their importance are still unknown. Here we suggest a method for determining crucial Pol II TF interactions by relating electromagnetic imaging to computer simulations. Results will be able to delineate individual amino acids responsible for maintaining the spatial organization of the proteins in vitro. The simulation-based study will be leveraged to explore the tolerance of maintaining these interactions when encountered with different phosphorylation states of CTD. A proof-of-concept study is then described which will demonstrate an ability to actively target IDRs to stabilize the protein interactions. While the results here will be comprehensive for four TFs of interest (RECQL5, SCAF4, SCAF8, and the SOSS1 complex), the methodology can then be expanded to characterize a library of over 400 TFs. Such a project has the potential to not only further our understanding of CTDs function, but also pave a way for designing synthetic treatments that can regulate the transcription process.

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-WIDERA-2023-TALENTS-02

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Coordinator

Masarykova univerzita
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 438,72
Address
Zerotinovo namesti 9
601 77 Brno
Czechia

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Region
Česko Jihovýchod Jihomoravský kraj
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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