Small proteins and dual RNA regulators regulating collective behaviors and carbon metabolism in Vibrio cholerae

小蛋白和双 RNA 调节因子调节霍乱弧菌的集体行为和碳代谢

• 批准号: 379644638
• 负责人: Professor Dr. Kai Papenfort
• 金额: --
• 依托单位: Professur für Mikrobielle Genregulation
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/379644638?language=en
• 关键词: Small; proteins; dual; RNA; regulators

The annotation of microbial genomes typically relies on the prediction of open reading frames (ORFs) with a minimal length requirement. While setting a lower limit for ORF length has led to a strong decrease in false positive gene annotations, it also resulted in an underrepresentation of small protein genes that we now know play important roles in microbial physiology. This strategy also failed to identify the so-called nested ORFs produced from within larger ORFs, as well as dual RNA regulators, which contain a base-pairing function and a small protein. In the previous funding period of this program, we have used ribosome profiling to identify small proteins in the major human pathogen, Vibrio cholerae. These studies resulted in the discovery of dozens of small proteins, including several examples of nested ORFs, and dual RNA regulators. Detailed analyses of one dual RNA, named VcdR (Vibrio cholerae dual RNA regulator), revealed a central role of this regulator in carbon metabolism control of V. cholerae. We next aim to understand the molecular underpinnings of VcdR-mediated gene regulation, as well as the roles of other small proteins in important collective behaviors such as quorum sensing, biofilm formation and virulence. Together, the work outlined in this proposal will further expand our view on the functions of small proteins in V. cholerae with a focus on yet only poorly studied examples contained in dual RNAs and nested ORFs.

微生物基因组的注释通常依赖于具有最小长度要求的开放阅读框（ORF）的预测。虽然为ORF长度设定下限导致了假阳性基因注释的大幅减少，但它也导致了我们现在知道在微生物生理学中发挥重要作用的小蛋白基因的代表性不足。这种策略也未能识别出从较大ORF中产生的所谓嵌套ORF，以及含有碱基配对功能和小蛋白质的双RNA调节子。在该项目的前一个资助期内，我们已经使用核糖体分析来识别主要人类病原体霍乱弧菌中的小蛋白。这些研究发现了数十种小蛋白，包括嵌套ORF和双RNA调节子的几个例子。对一种名为VcdR（霍乱弧菌双RNA调节子）的双RNA的详细分析揭示了该调节子在霍乱弧菌碳代谢控制中的核心作用。我们接下来的目标是了解VcdR介导的基因调控的分子基础，以及其他小蛋白在重要的集体行为中的作用，如群体感应，生物膜形成和毒力。总之，本提案中概述的工作将进一步扩大我们对霍乱弧菌中小蛋白功能的看法，重点是双RNA和嵌套ORF中包含的研究不足的例子。