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Structural basis of co-transcriptional pre-mRNA 3’-end processing

Project description

Co-transcriptional pre-mRNA 3’-end processing

RNA transcribed by RNA polymerase II (Pol II) undergoes many modifications to become mature mRNA. Among the key steps is the addition of the poly-adenine (poly-A) tail, which involves cleavage of the pre-mRNA from the growing RNA chain and the subsequent polyadenylation by a poly-A polymerase. These events are known as 3’-end processing and are the least understood steps of mRNA biogenesis. The EU-funded POL2-TERM project will investigate the transcription and the 3’-end processing to understand how poly-A tails are added onto pre-mRNA during Pol II transcription. The goal of the project is to define the mechanistic basis for the essential step in mRNA biogenesis and to understand human diseases that result from aberrations in RNA synthesis and processing.

Objective

RNAs transcribed by RNA polymerase II (Pol II) undergo numerous modifications before becoming export competent mature mRNA. One key step is the addition of the poly-adenine (poly-A) tail, which involves cleavage of the pre-mRNA from the growing RNA chain and the subsequent polyadenylation by poly-A polymerase. This cascade of events is known collectively as 3’-end processing and is one of the least understood steps of mRNA biogenesis. Pol II plays a vital role in recruiting and assembling the 3’-end processing machinery onto the nascent RNA, but the structural basis of transcription-coupled 3’-RNA processing is yet to be elucidated. This project aims to bring together the fields of transcription and 3’-end processing in order to understand how poly-A tails are added onto pre-mRNA in the context of actively transcribing Pol II. The most advanced methods of protein expression in recombinant systems as well as the extraction of complexes from native source will be coupled with state-of-the-art electron microscopy analysis to determine the structural basis of co-transcriptional 3’-end processing. Complementary biophysical methods will be used to map macromolecular interactions, and biochemical assays will be conducted to measure the impact of mutations introduced to characterize this fundamental biological process. The goal of this work is to provide the mechanistic basis for this essential step in mRNA biogenesis, and to understand human diseases that are resulted from aberrations in RNA production and processing.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
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.

€ 162 806,40
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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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.

€ 162 806,40
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