Project description
Understanding miRNA functions in atherosclerosis
Atherosclerosis often results in cardiovascular disease (CVD), which is the leading cause of death globally. MicroRNA miR-126-5p has been found to bind to caspase-3 with the help of MEX3A, revealing new insights into miRNA function beyond the RNA-induced silencing complex. The ERC-funded MONOFUN-CV project will examine the role of MEX3A in mouse atherosclerosis and its association with human risk variants. The research findings are expected to shed light on how MEX3A interacts with miR-126-5p and identify potential MEX3A-based therapies. It will also analyse miRNAs affected by MEX3A through techniques such as eCLIP, and explore the structural basis of MEX3A functions. Additionally, the project will investigate the interactions between miR-126-5p and caspase-3.
Objective
Atherosclerosis is the major underlying pathology of cardiovascular diseases (CVD), which remain the leading cause of death worldwide. The relevance of miRNAs in vascular biology, atherosclerosis and CVD has been well established. Our discovery of an aptamer-like binding of an endogenous miRNA to proteins, namely that of nuclear miR-126-5p to caspase-3, as facilitated by the RNA-binding protein MEX3A has extended the classical paradigm of miRNA function in the RISC, adding a new layer to the mechanisms enacted by miRNAs. Taking MEX3A as a starting point, MONO-FUN-CV aims to (1) characterize cell-specific contributions of MEX3A to mouse atherosclerosis and an association of MEX3a risk variants with human atherosclerosis, to dissect the specificity of its cross-talk with miR-126-5p, and to unravel potential MEX3A-based therapeutic options; we will (2) conduct an unbiased analysis of miRNAs affected by MEX3A (e.g. by eCLIP), elucidate the structural basis and mechanisms controlling MEX3A functions, e.g. ternary complex formation with AGO2, nuclear shuttling, and involvement of other adaptors (proteins, RNA); and (3) we will clarify structural bases and sequence requirements of miR-126-5p interactions with caspase-3, and its physiological relevance using novel in vivo models, as well as screen other miRNAs and proteins engaging in functional interactions, such as miR-210-5p and HIF-1α, to define templates for novel molecular modulators, e.g. aptamers. All aims include unbiased strategies to discover related miRNAs (e.g. nuclear, MEX3A-interacting) and adaptors contributing to the control of protein functions. These aims are highly interconnected and may enable groundbreaking insights into non-canonical mechanisms of miRNAs and their translation into novel approaches for therapeutic targeting of CVD and beyond.
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.
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pathology
- 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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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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(opens in new window) ERC-2024-ADG
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80539 Planegg
Germany
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