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The role of nuclear architectural RNAs in the long-term maintenance of the neural epigenome

Project description

Exploring the role of RNAs in neuronal ageing

Evolutionary higher organisms including humans exhibit limited neural regeneration capacity. This indicates that neurons have an inherent longevity. Understanding the underlying mechanisms that enable neurons to retain their function is central to the treatment of neurological diseases. The ERC-funded NEUTIME project focuses on the role of long-lasting nuclear RNAs in epigenetic process regulation. The working hypothesis is that long-retained nuclear RNAs interact with chromatin to preserve epigenetic regulation, a process that declines with ageing. Researchers aim to identify the implicated RNAs and study their maintenance mechanisms as well as their role in age-related neurological disorders.

Objective

Neurons in the brain must function for a life-time with limited replacement; thus, they need to robustly maintain their identity and function. Understanding the mechanisms underlying the longevity and persistence of neurons will be key for preventing and treating age-related neurological diseases. By focusing on epigenetic mechanisms regulated by nuclear RNAs, the project aims at understanding the fundamental mechanisms underlying the long-term maintenance of neural identity and their biological roles in the development of age-related vulnerability. The successful completion of this proposal will uncover novel roles of RNAs in long-term epigenetic regulation, and key biological links between epigenetic dysregulation and age-related pathological development.
We recently discovered that some nuclear RNAs in rodent brains do not turn over for two years. These RNAs are maintained in a neural cell type-specific manner and are mainly localized around heterochromatin. Through a targeted approach, satellite RNA was found to be one of the stable nuclear RNAs and is critical for the maintenance of heterochromatin. Based on this finding, the proposed project aims to test the specific hypothesis that neural cells possess several long-retained nuclear RNAs which interact with chromatin to stabilize cell type-specific epigenetic regulation, but that they deteriorate as a result of aging.
To address this question, we will use an interdisciplinary approach. First, the molecular identity of long-retained nuclear RNAs will be probed globally using deep sequencing. In parallel, mechanisms responsible for maintaining RNAs will be investigated Second, the roles of the nuclear RNAs and associated complexes we identify in maintaining cell type-specific epigenetic regulation will be investigated using neurobiological, epigenomic and biochemical approaches. Efforts will be directed toward understanding the roles of nuclear RNAs in pathophysiological brain aging.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN-NUERNBERG
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.

€ 1 999 970,00
Address
FREYESLEBENSTRAßE 1
91058 ERLANGEN
Germany

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Region
Bayern Mittelfranken Erlangen, Kreisfreie Stadt
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.

€ 1 999 970,00

Beneficiaries (1)

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