Deconstructing and Rewiring RNA-RBP regulatory networks

rna结合蛋白（rbp）是基因表达程序的关键调控因子。它们调节RNA生命的各个方面，包括转录、剪接、修饰、定位、稳定性、翻译和衰变，因此，这些rbp - rnannet中的扰动是许多疾病起源的基础。最近基于蛋白质组学的研究已经极大地扩展了rbp的种类到数千种，发现了非常规的rbp，如“兼职”rna结合活性的代谢酶或rna“核素调节”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的细胞稳态调节提供了一个全新的维度。RBP-ReguNet的设想是利用这些新发现来确定一系列无法治愈的疾病的药物靶点，包括癌症、神经系统疾病、肝脏疾病和传染病。我们在RBP-ReguNet的目标是创建一个基于基础研究但对临床翻译有强大影响的高水平培训计划。RBP- regunet将提供先进的多学科科学培训，从计算、结构、分子和细胞生物学到药物化学和药理筛选，为下一代欧洲研究人员提供跨部门环境，以追求雄心勃勃和高收益的研究，开发基于RBP生物学的新疗法。他们将接受一系列核心和最先进的学科研究技能、互补的可转移技能以及借调给非学术合作伙伴的创业技能的培训，共同的重点是发现可操作的目标。这个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.