Project description
RNA polymerase and transcription: biochemical and structural investigations
Gene expression begins with DNA transcription, during which the DNA message is copied onto a new molecule, messenger RNA, by the universally conserved enzyme RNA polymerase (RNAP). This step is essential to the healthy functioning of organisms and is implicated in a growing number of diseases. Despite its importance and considerable progress, the process is still incompletely understood. The ERC-funded TRANSREG project will use advanced biochemical and structural approaches combined with studies of the dynamics of RNAP to address critical questions concerning RNAP dynamics during processes that regulate transcription. Although focused on bacterial RNAP, insight and experience could pave the way to similar studies in more complex organisms.
Objective
During the first step of gene expression, a universally conserved enzyme called RNA Polymerase (RNAP) transcribes RNA from a DNA template in every cell. Transcription is a fundamental, yet incompletely understood process. Because of its central role, the bacterial transcription machinery is also a prime drug target. Crystal structures of RNAP core as well as RNAP elongation complexes (ECs) have revolutionized our understanding of transcription. This groundwork paved the way to address more complex questions regarding the regulation of transcription. Transcriptional regulation impacts every aspect of biology including a growing list of human diseases. Transcriptional pausing, a temporary interruption of transcription during elongation, plays a major role in regulating gene expression in pro- and eukaryotes. A full and mechanistic understanding is crucial and requires a combination of structural and biochemical studies. This is where the proposed work will contribute.
Our goal is to understand how transcription factors modulate RNAP during the elongation phase.
Biochemical and structural approaches (X-ray crystallography and single particle cryo-EM) will be used to gain detailed insights on the regulation of transcription by protein factors and non-coding RNAs (ncRNAs). To complement the results, an experimental system will be established using Fluorescence Resonance Energy Transfer (FRET) to study the dynamics of RNAP. This system will allow us to address questions concerning RNAP dynamics during processes that regulate transcription.
Specifically, we propose 3 aims:
1.: Investigate the role of transcription elongation factors that modulate RNAP pause behavior and couple transcription and translation
2.: Study the role of RNAs that regulate transcription
3.: Establish an experimental system to study RNAP dynamics using FRET
The proposed work will lay the groundwork and prepare the team to address similar questions in higher organisms in the future.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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
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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.
ERC-STG - Starting Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2015-STG
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67404 Illkirch Graffenstaden
France
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