Mechanisms of intracellular mRNA trafficking in ALS

In healthy motor neurons, RNA molecules — messengers that help cells produce the proteins they need — are carefully transported to specific locations within the cell. This process is highly organized and can change in response to stress or other signals. In ALS, however, this system appears to be disrupted, and RNAs may end up in the wrong places, potentially contributing to disease progression. Research shows that certain parts of an RNA molecule act like an “address label” that directs it to the correct location in the cell, but these address signals are not yet fully understood, especially in the context of ALS.

In this project, Dr. Binan and the team will develop a high-throughput screening method that can examine hundreds of RNA sequences at once. This will allow them to identify which RNA segments act as address signals and determine how they guide RNA molecules to different parts of the cell. Understanding these signals will help reveal how RNA placement becomes disrupted in ALS.

In the long term, these discoveries could support the development of new ALS treatments aimed at correcting RNA misplacement in affected cells. The tools and methods created through this work will also enable future research into other important roles that RNA regions play in cellular function.

In 2006, the landmark discovery that 97% of ALS cases had abnormalities in the biology of a protein called TDP-43, which plays several important roles in how cells manage their RNA, significantly shifted fundamental ALS research. Since then, several researchers have highlighted abnormal RNA biology as a likely critical process underlying motor neuron health in the disease. ALS Canada funding has significantly impacted the field’s continually evolving understanding of these complex systems.