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RNA DISEASES

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UNDERSTANDING THE CAUSES OF THE RNA GAIN OF FUNCTION DISEASES

"It is now increasingly clear that most of our genome is transcribed, but that only a small portion is associated with protein coding gene. Indeed, recent analysis indicate that long non-coding RNA outnumbered by five fold the cod... ver más

28/02/2018

CERBM-GIE

1M€

Presupuesto del proyecto: 1M€

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CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET M... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2018-02-28 No tenemos la información de la convocatoria

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Líder del proyecto

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET M... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto "It is now increasingly clear that most of our genome is transcribed, but that only a small portion is associated with protein coding gene. Indeed, recent analysis indicate that long non-coding RNA outnumbered by five fold the coding RNA sequences. Despite this abundance, very little is known on the function of these long non-coding RNA. The aim of this proposal is to understand the function of pathological long non-coding RNA. We will first focus our studies on the RNA gain-of-function diseases. These genetic diseases are caused by the pathogenic expansion of nucleotide repeats, which are transcribed into long non-coding RNA that titrate and sequester specific RNA-binding proteins, leading to molecular changes ultimately resulting in the symptoms of these pathologies. The RNA gain-of-function diseases include the most common muscular dystrophies in adult: the Myotonic Dystrophies of type 1 and type 2 (DM), the common neurodegenerative Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) and the rare, but deleterious, Spinocerebellar Ataxia 10, 31 and 36 (SCA10, SCA31 and SC36). We propose to : 1 – Identify the proteins sequestered by theses expanded RNA repeats. 2 – Identify the molecular causes of DM, FXTAS and SCA diseases in iPS neuronal cell model and mouse models. 3 – Identify pharmacological compounds able to reverse the toxic effects of these RNA. Importantly, these RNA gain of function diseases present identical symptoms to other pathologies that are much more common and tremendously challenging to our society (for example the tremor in FXTAS is similar to the one observed in Parkinson; the cognitive impairment, the demence and the neurodegeneration found in FXTAS are present in Alzheimer Disease; the heart failure, which is a leading cause of morbidity in Europe is a cardinal symptom of DM; etc.). THUS, ELUCIDATING THE MOLECULAR CAUSES OF THESE RNA DISEASES MAY HELP TO UNDERSTAND THE PATHOLOGY OF OTHER COMMON AND CHALLENGING DISEASES."

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