"Structural Dynamics Control the MicroRNA Maturation Pathway"
Dr. François Major (U de M)

MicroRNAs (miRNAs) are crucial gene expression regulators and first-order suspects in the development and progression of many diseases. Comparative analysis of cancer cell expression data highlights many deregulated miRNAs. Low expression of miR-125a was related to poor breast cancer prognosis. Interestingly, a single nucleotide polymorphism (SNP) in miR-125a was located within a minor allele expressed by breast cancer patients. The SNP is not predicted to affect the ground state structure of the primary transcript or precursor, but neither the precursor nor mature product is detected by RT-qPCR. How this SNP modulates the maturation of miR-125a is poorly understood. Here, building upon a model of RNA dynamics derived from nuclear magnetic resonance studies, we developed a quantitative model enabling the visualization and comparison of networks of transient structures. We observed a high correlation between the distances between networks of variants with that of their respective wild types and their relative degrees of maturation to the latter, suggesting an important role of transient structures in miRNA homeostasis. We classified the human miRNAs according to pairwise distances between their networks of transient structures.

Dr. Francois Major is Full Professor of Computer Science  and IRIC Principal investigator at the Université de Montréal since 2005. In 2010, he has won Prize Urgel-Archambault from ACFAS. He completed his graduate studies in Université de Montréal and postdoctoral training at National Center for Biotechnology of the National Institutes of Health from 1990-1994. His lab combines RNA engineering and bioinformatics to study RNA structure and function. 

He is the guest of Dr. Heidi Muchall.