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人们能够发现出人意料的大量小RNA(SRNAs)及其蛋白质辅助因子，以及短开放阅读框架(SORF)。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节因子，并阐明了新的调节机制和概念。然而，在其他细菌谱系中，生理、基因含量和调控基因表达的机制非常不同。因此，在具有不同生活方式和分子机制的进化遥远的细菌中，必须研究sRNA和sORF的机制。IntRNAReg将使用化脓性和产毒性革兰氏阳性病原体金黄色葡萄球菌和光合胞菌6803。我们将生成RNA相互作用组图，并表征新发现的sRNA结合蛋白和sRNAs编码的sORF的功能。综合的统计和计算分析将产生关于特定调控和生理环境的信息，并将有助于回答几个问题：哪些基因受多个sRNA调控，并作为调控中心？由sRNAs整合的压力和环境变化、代谢适应和毒力表达之间的联系途径是什么？SRNAs及其相互作用蛋白介导的调控事件有多复杂？SRNAs，包括携带sORFs的sRNAs，对种群行为和宿主-病原体相互作用有贡献吗？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，描述与毒力和适应环境变化相关的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.