CORDIS
EU research results

CORDIS

English EN

UNDERSTANDING THE CAUSES OF THE RNA GAIN OF FUNCTION DISEASES

Objective

"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."
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Principal Investigator

Nicolas Charlet Berguerand (Dr.)

Host institution

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE

Address

Rue Laurent Fries 1
67404 Illkirch Graffenstaden

France

Activity type

Research Organisations

EU Contribution

€ 1 499 920

Principal Investigator

Nicolas Charlet Berguerand (Dr.)

Administrative Contact

Steve Brooks (Dr.)

Beneficiaries (1)

Sort alphabetically

Sort by EU Contribution

Expand all

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE

France

EU Contribution

€ 1 499 920

Project information

Grant agreement ID: 310659

Status

Closed project

  • Start date

    1 March 2013

  • End date

    28 February 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 499 920

  • EU contribution

    € 1 499 920

Hosted by:

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE

France