An integrated investigation of regulatory RNAs and their interacting proteins in bacteria models

最近的全基因组策略和计算方法使得发现意想不到的大量小rna （sRNAs）、它们的蛋白质辅助因子和短开放阅读框（sorf）成为可能。开创性的工作，主要是在革兰氏阴性模式细菌中，将许多这些新的基因产物表征为重要的调控因子，并阐明了新的调控机制和概念。然而，在其他细菌谱系中，生理、基因含量和调节基因表达的机制是非常不同的。因此，必须在具有不同生活方式和分子机制的进化遥远细菌中研究基于sRNA和sORF的机制。IntRNAReg将利用产化脓性和产毒素的革兰氏阳性病原体金黄色葡萄球菌和光合合胞菌6803。我们将生成RNA相互作用组图，并表征新鉴定的srna结合蛋白和由srna编码的sORF的功能。综合统计和计算分析将产生关于特定调节和生理设置的信息，并将有助于回答几个问题：哪些基因由多个srna调节并充当调节中心？通过sRNAs整合应激与环境变化、代谢适应和毒力表达的途径是什么？sRNAs及其相互作用蛋白介导的调控事件的复杂性是什么？包括携带sorf的sRNAs在内的sRNAs是否对种群行为和宿主-病原体相互作用有贡献？合作伙伴将结合他们在计算和RNA生物学、分子微生物学和微生物系统生物学方面的互补专业知识，描绘与毒力和环境变化适应相关的sRNAs及其蛋白质伙伴的功能，为治疗和生物技术开辟新的途径。

Recent genome-wide strategies and computational approaches enabled the discovery of an unexpectedly high number of small RNAs (sRNAs), their protein co-factors, and of short open reading frames (sORFs). Pioneering work, mainly in Gram-negative model bacteria, characterized many of these novel gene products as important regulatory factors and elucidated novel regulatory mechanisms and concepts. However, physiology, gene content and mechanisms to regulate gene expression are extremely diverse in other bacterial lineages. Therefore, the landscape of sRNA and sORF based mechanisms has to be studied in evolutionarily distant bacteria that possess different lifestyles and molecular machineries. IntRNAReg will use the pyogenic and toxigenic Gram-positive pathogen Staphylococcus aureus and the photosynthetic Synechocystis 6803. We will generate RNA interactome maps, and characterize the functions of newly identified sRNA-binding proteins and sORF encoded by sRNAs. Integrative statistical and computational analysis will generate information on the particular regulatory and physiological settings and will help to answer several questions: Which genes are regulated by multiple sRNAs and serve as regulatory hubs? What are pathways linking stress and environmental changes, metabolism adaptation and virulence expression integrated by sRNAs? What is the complexity of the regulatory events mediated by sRNAs and their interacting proteins? Do sRNAs including sRNAs carrying sORFs contribute to the population behavior and to host-pathogen interactions? The partners will combine their complementary expertise at the interface of computational and RNA biology, molecular microbiology, and microbial systems biology to delineate the functions of sRNAs and their protein partners associated with virulence and acclimation to environmental changes opening new avenues for therapy and biotechnology.