Project description
The fate of genetic messages
The cells in our body constantly produce molecular messages that carry instructions for making proteins. Cells must ensure these messages are functional and destroy those that are faulty. Although many diseases are associated with errors in this quality control process, little is known about the underlying mechanisms. The ERC-funded FATERNA project is investigating how cells make this critical decision, focusing on the role of RNA splicing in directing human messages towards either productive use or degradation. Using cryo-electron microscopy, molecular biology and super-resolution imaging, researchers will visualise the molecular decision points responsible for processing these messages. Project results will provide important insights into a fundamental biological process with broad implications for understanding cell function and disease. .
Objective
Messenger RNA (mRNA) is critical for transferring information from DNA to protein, a process that requires a series of tightly orchestrated steps. During these steps, mRNAs are classified as either functional or faulty, and directed towards biogenesis or degradation. This ensures the efficient and faithful expression of protein-coding genes. Yet, the mechanisms that decide the fate of mRNAs remain unclear. Prior work and our preliminary data show that RNA splicing plays a critical role in making this decision, by committing functional mRNAs towards packaging into ribonucleoprotein complexes (mRNPs) and directing faulty mRNAs towards degradation. Although recent studies have revealed individual aspects of RNA splicing, packaging, and decay, it remains unclear how these processes work together to distinguish functional from faulty mRNPs and determine their fate. Here, I propose to visualize key mRNP processing intermediates from human cells to advance our understanding of mRNA fate control toward biogenesis (aim 1) or decay (aim 2). Central to our efforts is the visualization of large and dynamic precursor mRNP complexes undergoing splicing and packaging (aim 1) or splicing and decay (aim 2) using state-of-the-art cryo-electron microscopy, tomography, and protein crosslinking. This leverages our expertise and preliminary data for the integrative study of endogenous protein-nucleic acid complexes. Our research will generate new hypotheses for how mRNP biogenesis and degradation are achieved, which we will probe in targeted in vitro and in vivo structure-function experiments, including by the super-resolution imaging of mRNAs in cells. This work will consolidate three areas of RNA biology – splicing, packaging, and decay – and promises groundbreaking insights into the mechanisms that control precursor mRNA fate.
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 physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
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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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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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.
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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.
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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-2025-COG
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1030 Wien
Austria
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