Studying the involvement of cell surface RNA binding proteins in ALS pathogenesis

RNAs and their sidekicks, RNA-binding proteins (RBPs), play essential roles in cellular functions by forming complexes that regulate gene expression. A common feature of ALS is abnormal changes in RNA metabolism and their dynamics, contributing to disease progression. While previous studies have focused on studying RNA and RBPs inside cells, recent work showed that these factors can also be localized to their surface, where they may play a role in cell-to-cell recognition and communication. The exact biological roles and disease implications of these cell surface RBPs (csRBPs) are still not understood.

In this project, Dr. Lécuyer and his team aim to shed light on the roles of these cell surface localized RNA factors and explore how they affect disease progression. They propose that csRBPs might play a role in ALS by enabling the transmission of toxic signals between cells. To study this, they will compare healthy cells and ALS models to see how RBPs reach the cell surface. Additionally, they will further explore csRBPs’ role in cell-to-cell communication and the transmission of toxic signals and stress-related molecules between cells.

Improving our understanding of this RNA world at the cell surface could help inform future therapeutic strategies to interrupt undesirable cell-to-cell communication, a hallmark of ALS.

Collaborators: Dr. Christine Vande Velde

Since the connection of TDP-43 to ALS in 2006, several other ALS genes have been identified, highlighting abnormal RNA biology as a likely critical process underlying motor neuron health in the disease. ALS Canada funding over the years has significantly impacted the field’s continually evolving understanding of these complex systems.