Team 5 : (S.Millevoi)RNA-binding proteins and post-transcriptional regulation in cancer
Alteration of post-transcriptional gene expression regulation is a hallmark of cancer. RNA-binding proteins (RBPs) are master regulators required for all post-transcriptional processes, including pre-mRNA splicing, polyadenylation, mRNA stability and translation. These factors allow dynamic regulation in normal and various stress conditions, and contribute to deregulations in the RNA metabolism of cancer cells. They can also directly impact genome instability by establishing a direct link between DNA- and RNA-mediated processes. RBPs recognize specific elements of diverse sequences and structures. Among these, RNA G-quadruplex structures have been shown to affect the expression of cancer relevant genes by modulating post-transcriptional steps.Our research focuses on understanding the role of RBPs in post-transcriptional gene expression reprogramming in response to stress and to the deregulation associated to cancer pathobiology and resistance to treatments. We explore the role of RNA-protein interactions in cancer by integrating multiple layers of information based on multidisciplinary approaches, including 1) molecular mechanisms of regulation 2) genome-wide analysis of post-transcriptional regulations and of RNA-protein interactions 3) pre-clinical in vitro (spheroids) and in vivo analysis (xenografts models) and 4) clinical data from patients (Tissue microarray, TMA). We are also interested in developing small molecules that target cancer relevant post-transcriptional processes directed by specific RNA-protein interactions.
RNA-protein interactions, Pre-mRNA processing, mRNA translation and stability, G-quadruplex, DNA damage response, metastasis, drug resistance, cancer gene expression