Régulation post-transcriptionnelle de l'ARN par l'ARN des protéines de liaison dans la sclérose latérale amyotrophique (SLA)


Chantelle Sephton

Centre de recherche de l'Institut universitaire en santé mentale de Québec


Domaine : neurosciences, santé mentale et toxicomanies

Programme chercheurs-boursiers - Junior 1

Concours 2015-2016

Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease. ALS patients suffer from the degeneration of neurons involved in motor function, leading to muscle weakness, paralysis and eventually death within 3 to 5 years of disease onset. There is no cure or effective therapies for those who suffer from ALS and the mechanism by which the disease occurs is not understood. There is evidence to suggest that ALS is caused by alterations in the production of proteins essential for motor neuron function. This is based on the finding that RNA-binding proteins (regulators of RNA processing into protein) are found in pathological protein aggregates in neurons that control motor function. In a subset of ALS patients that genetically inherit the disease, RNA-binding proteins are mutated. Moreover, these RNA-binding proteins regulate the production of essential proteins important for healthy motor neuron function. However, these findings alone do not explain if altered RNA-binding protein function can affect the processing of RNA into protein or if these changes would lead to the degeneration of motor neurons.

The major goals of our research is to determine how processing of RNA is altered in ALS and determine new therapeutic approaches to finding a cure for the disease. We will accomplish this by studying RNA-binding proteins that are mutated in ALS and assess their function. We will use our novel mouse models that develop ALS symptoms and cell culture models of ALS to study the function of RNA-binding proteins and the efficacy of therapeutics. Relevant findings will be confirmed in ALS patient samples. The findings from these studies will advance our understanding of how altered RNA regulation can cause ALS and we will use this information to develop targeted therapeutics to cure the disease.