Grant: Operating Grant

Over the past few years, an important new class of molecules influencing cell behavior was discovered: the microRNAs. About one thousand of these little regulators are at work in human cells, and they have been implicated in almost every biological process, but also in numerous diseases including cancer. MicroRNAs mostly act as repressors of genes by directly binding to a portion of the messengers of genes (mRNAs) termed the 3 prime untranslated region (3'UTR). Understanding exactly how microRNA function in controlling gene expression represents an important new frontier in biomedical research. With this grant proposal, we put forward experiments aimed at understanding how microRNA interact with sites on mRNAs, and more precisely how they interact with one another. Using molecular biology and genomic tools, we will determine how sites interact synergistically, a configuration of microRNA sites coined synmiRS. We will define the parameters that govern such interactions, and probe the mechanism underlying the cooperative potentiation of gene silencing directed by the miRNA silencing machinery. Finally, we will examine how the remolding of the 3'UTR portions of mRNAs affect the interactions of microRNA-binding sites, and their capacity to modulate gene activity. Better understanding of how microRNA interact with mRNAs will allow to discern the biologically important microRNA-binding sites in the genome from weak or non-functional ones. Hence, this project offers much promise in grasping the impact of microRNAs in important biological processes, and their roles in diseases.