Deconstructing and Rewiring RNA-RBP regulatory networks

RNA结合蛋白(RNAbindingProteins，RBPs)是基因表达的重要调控因子。它们调节RNA生命的方方面面，包括转录、剪接、修饰、定位、稳定性、翻译和衰退，因此，这些RBP-RNN网络中的扰动是许多疾病的根源。最近基于蛋白质组学的研究极大地扩大了限制性商业惯例的范围，发现了非传统的限制性商业惯例，如代谢酶在RNA结合活性上的‘兼职’或RNA“核调节”蛋白质功能。这代表了先前设想的更广泛的生物控制层，这为依赖RBP的细胞内稳态调控提供了一个全新的维度。RBP-RguNet的构想是利用这些新发现来确定一系列无法治疗的疾病的可用药靶点，包括癌症、神经疾病、肝病和传染病。我们在RBP-RguNet的目标是在基础研究的基础上创建一个高水平的培训计划，并对临床翻译产生强大的影响。RBP-RguNet将提供先进的多学科科学培训，范围从计算、结构、分子和细胞生物学到药物化学和药理筛选，面向跨部门环境中的下一代欧洲研究人员，在基于RBP生物学的新疗法开发方面进行雄心勃勃和高收益的研究。他们将接受一系列核心和最先进的特定学科的研究技能、补充的可转让技能和借调到非学术合作伙伴的创业技能方面的培训，共同关注发现可行的目标。这一卓越的网络将推动蛋白质-RNA相互作用领域的知识边界，同时为下一代学生提供成为该领域未来领导者的技能。

RNA-binding proteins (RBPs) are critical regulators of gene expression programs. They regulate all aspects of RNA life, includingtranscription, splicing, modification, localization, stability, translation and decay, and consequently, perturbations in these RBP-RNAnetworks underlie the origin of many diseases. Recent proteomics-based studies have vastly expanded the repertoire of RBPs to thethousands, 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, whichadds an entirely new dimension to RBP-dependent regulation of cellular homeostasis. RBP-ReguNet has been conceived to leveragethese new discoveries to identify druggable targets for a range of untreatable diseases, including cancer, neurological disorders, liverdiseases and infectious disease. Our ambition in RBP-ReguNet is to create a high-level training program based on basic research butwith a strong impact on clinical translation. RBP-ReguNet will provide advanced multidisciplinary scientific training that spans fromcomputational, structural, molecular and cellular biology to medicinal chemistry and pharmacological screening, to the nextgeneration of European researchers in an intersectoral environment to pursue ambitious and high gain research on the developmentof 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 todiscover actionable targets. This network of excellence will push the boundaries of knowledge in the protein-RNA interactionsuniverse, and at the same time provide the next generation of students with the skills to become future leaders in the field.