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Nuclear mRNA Packaging and mRNP Architecture

Objective

An important step of gene expression is the formation of a messenger ribonucleoprotein particle (mRNP). The messenger RNA (mRNA) is synthesized by RNA polymerase II transcribing a protein-coding gene. The mRNA is processed, i.e. capped, spliced and polyadenylated, and packaged into an mRNP by binding of RNA-binding proteins (RBPs). The RBPs bound to the mRNA are essential for the stability of the mRNP, control nuclear mRNA export and often determine cytoplasmic processes such as mRNA localization, translation and decay. Thus, the formation and composition of an mRNP is important for the posttranscriptional control of gene expression. Despite its essential nature, the mechanism of nuclear mRNP packaging and the architecture of an mRNP are still poorly understood due to the fact that mRNPs contain many different mRNAs. The overall goal of this proposal is to elucidate the mechanism of mRNP formation and the molecular structure of an mRNP. Specifically,
in aim 1, we will determine and quantify the protein composition of a specific mRNP including different stages during its biogenesis,
in aim 2, we will illuminate the molecular mechanism of mRNP packaging and
in aim 3, we will elucidate the architecture of an mRNP by cross-linking mass spectrometry and electron microscopy.
These aims will be achieved by combining novel RNP purification strategies and the powerful biochemistry of the model organism S. cerevisiae to purify a specific mRNP with recent advances in high-end mass spectrometry and electron microscopy. In summary, the expected results of this project will show the architecture of an mRNP in its dynamic nature. mRNP packaging will be understood for the first time on a mechanistic as well as structural level. Thus, the results of this project will break new ground in our understanding of this fundamental cellular process and will also provide insights into how defects in this process lead to disease.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2017-COG

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Host institution

JUSTUS-LIEBIG-UNIVERSITAET GIESSEN
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.

€ 1 991 387,50
Address
LUDWIGSTRASSE 23
35390 GIESSEN
Germany

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Region
Hessen Gießen Gießen, Landkreis
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 991 387,50

Beneficiaries (1)

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