Date: Vendredi 20 février 2026
Heure: 11:00
Lieu: Salle F-1455
Centre de recherche CERVO
Quebec, Quebec G1J 2G3Une présentation de:Mathieu Flamand

Centre de Recherche du CHU de Québec – Université Laval

RNA modifications have emerged as a pervasive feature of cellular mRNAs with diverse impacts on gene expression. N6-methyladenosine (m6A), the most abundant internal mRNA modification, is involved in the control of mRNA processing, stability, and translation and has important roles within the nervous system. Studies in animal models have revealed severe neurodevelopmental and cognitive deficits linked to disruptions in mRNA modification machinery. Moreover, recent research has shown that levels of m6A are altered in several neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Despite this, the precise molecular mechanisms by which m6A mediates these effects are still not understood. The primary research focus of my group is to unravel the intricate mechanisms by which m6A regulates neuronal functions, and exploring the consequences of alterations in the m6A regulatory networks in neurodegenerative diseases. Using transcriptomic methods and single-molecule localization studies, we first found that m6A contributes to the localization of select mRNAs to dendrites and axons in mouse hippocampal neurons. Through a unique RNA-editing method, we have discovered that distinct m6A readers, which are proteins that recognize m6A, have different effects on their targets. We propose that m6A readers interact with distinct proteins in both the soma and synapses, thereby locally regulating gene networks. We hypothesize that disruptions in these networks lead to impairments in synaptic function and contribute to the development of neurodegenerative disorders associated with cognitive impairment. Progress in this line of research critically rely on a better understanding of the local interactions and functions of RNA-binding proteins in the brain. However, the tools to identify interactions in neurites harbouring functional synapses are lacking. To overcome this obstacle, we are currently developing proximity labelling methods that will allow us to map protein-protein and protein-RNA interactions in neuronal projections in vitro and at synapses in vivo. By integrating biochemical assays, transcriptomic analyses, and advanced imaging techniques, we aim to elucidate the complex roles of m6A readers at synapses and understand how their functions are altered during neurodegeneration.