Deconstructing and Rewiring RNA-RBP regulatory networks

RNA-binding proteins (RBPs) are critical regulators of gene expression programs. They regulate all aspects of RNA life, including transcription, splicing, modification, localization, stability, translation and decay, and consequently, perturbations in these RBP-RNA networks underlie the origin of many diseases. Recent proteomics-based studies have vastly expanded the repertoire of RBPs to the thousands, uncovering unconventional RBPs such as metabolic enzymes ‘moonlighting’ in RNA-binding activity or RNAs “riboregulating” protein function. This represents a much broader layer of biological control that was previously envisaged, which adds an entirely new dimension to RBP-dependent regulation of cellular homeostasis. RBP-ReguNet has been conceived to leverage these new discoveries to identify druggable targets for a range of untreatable diseases, including cancer, neurological disorders, liver diseases and infectious disease. Our ambition in RBP-ReguNet is to create a high-level training program based on basic research but with a strong impact on clinical translation. RBP-ReguNet will provide advanced multidisciplinary scientific training that spans from computational, structural, molecular and cellular biology to medicinal chemistry and pharmacological screening, to the next generation of European researchers in an intersectoral environment to pursue ambitious and high gain research on the development of new therapies based on RBP biology. They will be trained in a range of core and state-of-the-art discipline-specific research skills, complementary transferable skills, and entrepreneurial skills by secondments to non-academic partners, with a common focus to discover actionable targets. This network of excellence will push the boundaries of knowledge in the protein-RNA interactions universe, and at the same time provide the next generation of students with the skills to become future leaders in the field.