Decoding RNA Organization to Drive Future Therapies

The term “gene expression” refers to the fundamental process by which cells produce the proteins necessary for our functioning from messenger RNA, which serves as a blueprint. Typically, researchers study this mechanism by extracting RNA molecules to analyze them holistically in a test tube. However, this method obscures a crucial reality: within a single cell, identical molecules can behave heterogeneously. For Daniel Zenklusen, a researcher at the University of Montreal, the challenge is therefore to observe each molecule individually in its natural environment, in order to grasp the true complexity of living organisms and to challenge scientific dogmas that are sometimes incomplete.

To achieve this, his laboratory is refining super-resolution microscopy and single-molecule detection technologies. These methods make it possible to visualize the structural organization of messenger RNAs (mRNAs) and their precursors, as well as other large complexes within cells. In particular, the research has revealed that mRNAs adopt more distinct conformations within cells than previously thought, and has highlighted the complex role of the nuclear pore in transporting mRNA from the nucleus, where it originates, to the site where proteins are synthesized. The team discovered that these pores are not all identical, suggesting specialized functions previously unimagined.

These discoveries open up major avenues in biomedical research. A better understanding of RNA transport is essential, as mutations in this process are linked to neurodegenerative diseases. Furthermore, studying RNA organization helps us understand the development of cancerous tumors. This knowledge is already crucial for mRNA-based therapies, such as COVID-19 vaccines. By fostering the development of a highly skilled workforce, Dr. Zenklusen’s work positions Quebec as a leader in therapeutic RNA research, promising future advances for numerous diseases.

References
Bensidoun, P., Reiter, T., Montpetit, B., Zenklusen, D., and Oeffinger, M. (2022). Nuclear mRNA metabolism drives selective basket assembly on a subset of nuclear pores in budding yeast. Molecular Cell, 82(20), 3856-3871.e6.

Adivarahan, S., Livingston, N., Nicholson, B., Rahman, S., Wu, B., Rissland, O. S., and Zenklusen, D. (2016). Spatial organization of single mRNPs at different stages of the gene expression pathway. Molecular Cell, 72(4), 727-738.https://pubmed.ncbi.nlm.nih.gov/26694838/

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