Deciphering the Roles of m6A and YTHDF Proteins in Synaptic Function and Plasticity

Date: Friday, February 20, 2026
Time: 11:00 a.m.
Location: Room F-1455
Centre de recherche CERVO
Quebec City, Quebec G1J 2G3

Presented by:
Mathieu Flamand
Centre de recherche du CHU de Québec – Université Laval

RNA modifications have emerged as a pervasive feature of cellular mRNAs, exerting diverse effects on gene expression. N6-methyladenosine (m6A), the most abundant internal mRNA modification, plays a key role in regulating mRNA processing, stability, and translation, and is critically involved in nervous system function. Studies in animal models have revealed severe neurodevelopmental and cognitive deficits associated with disruptions in mRNA modification machinery. In addition, altered m6A levels have been reported in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.

Despite these findings, the precise molecular mechanisms through which m6A exerts its effects remain unclear. The primary focus of our research is to unravel the mechanisms by which m6A regulates neuronal function and to investigate the consequences of disruptions in m6A regulatory networks in neurodegenerative disorders.

Using transcriptomic approaches and single-molecule localization studies, we first demonstrated that m6A contributes to the localization of specific mRNAs to dendrites and axons in mouse hippocampal neurons. Through a novel RNA-editing strategy, we further discovered that distinct m6A reader proteins—molecules that recognize and bind m6A—exert differential effects on their target transcripts.

We propose that m6A readers interact with distinct protein partners in both the soma and synapses, thereby locally regulating gene networks. We hypothesize that disruptions in these networks impair synaptic function and contribute to the development of neurodegenerative diseases associated with cognitive decline.

Advancing this field requires a deeper understanding of the local interactions and functions of RNA-binding proteins in the brain. However, current tools are insufficient to identify interactions within neurites containing functional synapses. To address this limitation, we are developing proximity-labeling approaches 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, our goal is to elucidate the complex roles of m6A reader proteins at synapses and their contribution to synaptic plasticity and brain health.