Understanding the molecular principles governing mRNP architecture
The GOVERNA project aims to elucidate the structure and function of eukaryotic mRNPs by purifying and analyzing their composition using advanced biochemical and imaging techniques.
Projectdetails
Introduction
Eukaryotic messenger ribonucleoprotein (mRNP) particles are the functional entities that carry genetic information to the protein synthesizing machinery. These ribonucleoprotein complexes are dynamic and diverse, as highlighted by the copious number of proteins and transcripts identified in global proteomic and transcriptomic studies.
Knowledge Gap
However, little is known about the composition and architecture of individual mRNPs, and how changes in mRNP structure relate to their function or to dysfunction. The GOVERNA project will address this gap in knowledge by purifying specific mRNPs and delving into their molecular and structural arrangement.
Methodology
With our preliminary data serving as a springboard, the project combines:
- Genomic tagging engineered to maintain the most physiologically relevant conditions.
- Biochemical methods developed to preserve the integrity of transient ribonucleoprotein assemblies.
- Mass spectrometry and cryo-electron microscopy to identify the composition and architecture of mRNPs.
Research Focus
We will zoom in on a set of paradigms in RNA biology that not only sample the breadth of mRNP diversity but are also powerful model systems for linking structural information and biological function.
Specific Investigations
We will investigate the molecular features in the three-dimensional organization of:
- Nuclear mRNPs from S. cerevisiae.
- Translationally repressed mRNPs in early developmental stages in D. melanogaster and X. laevis.
For mRNPs undergoing active translation, we will investigate the transitions of human beta-globin mRNPs in the course of a surveillance process connected to disease.
Expected Outcomes
By studying these examples, we will glean fundamental insights into global principles governing the packaging of mRNPs and the remodeling of their three-dimensional features throughout a transcript's life cycle. The cumulative output will illuminate a central node of eukaryotic gene expression that is also particularly timely and relevant given recent developments in mRNA-based therapeutics.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 2.171.250 |
Totale projectbegroting | € 2.171.250 |
Tijdlijn
Startdatum | 1-10-2022 |
Einddatum | 30-9-2027 |
Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EVpenvoerder
Land(en)
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