Deconstructing and Rewiring RNA-RBP regulatory networks

解构和重新连接 RNA-RBP 调控网络

• 批准号: EP/X029972/1
• 负责人: Alfredo Castello Palomares
• 金额: $ 33.8万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX029972%2F1
• 关键词: Deconstructing; Rewiring; RNA; RBP; regulatory

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.

RNA结合蛋白（RBP）是基因表达程序的关键调节因子。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-RNA网络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将RBP的库扩展到数千个，发现了非常规的RBP，例如在RNA结合活性或RNA“核糖调节”蛋白质功能中的代谢酶“兼职”。这代表了以前设想的更广泛的生物控制层，为RBP依赖的细胞稳态调节增加了一个全新的维度。RBP-ReguNet被认为是为了收集这些新发现，以确定一系列无法治疗的疾病的药物靶点，包括癌症，神经系统疾病，肝病和传染病。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烈影响的高水平培训计划。RBP-ReguNet将为跨部门环境中的下一代欧洲研究人员提供先进的多学科科学培训，涵盖计算、结构、分子和细胞生物学、药物化学和药理筛选，以追求雄心勃勃的高收益研究。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特定研究技能，互补的可转移技能和企业家技能的培训，并将其借调给非学术合作伙伴，共同关注发现可操作的目标。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。