The role of tmRNA in development of C. crescentus

tmRNA 在 C. crescentus 发育中的作用

• 批准号: 6884070
• 负责人: KENNETH C KEILER
• 金额: $ 28.71万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884070
• 关键词: Caulobacter; DNA replication; DNA replication origin; bacterial genetics; cell cycle; cell growth regulation; endoribonucleases; enzyme activity; enzyme substrate; gene expression; genetic promoter element; genetic regulation; genetic transcription; mass spectrometry; matrix assisted laser desorption ionization; messenger RNA; nucleic acid structure; plasmids; site directed mutagenesis; transfer RNA; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): Regulation of gene expression by noncoding RNAs (ncRNAs) is an emerging paradigm in biology. ncRNAs regulate a variety of processes, including transcription, translation, RNA modification, mRNA stability, RNA splicing, chromatin structure, and protein stability and activity, in a wide variety of organisms from bacteriophages to humans. Eukaryotic and prokaryotic genomes contain hundreds of uncharacterized ncRNAs, and these genes have been increasingly identified as the loci of mutations that cause developmental defects and several human diseases. One of the most interesting of these ncRNAs is tmRNA, a molecule with properties of both a tRNA and an mRNA, which intervenes in selected translation reactions; tmRNA recognizes selected translation complexes and enters the ribosome to mediate the addition of a peptide tag to the nascent polypeptide, targeting the protein for rapid degradation and releasing the ribosome and mRNA. This unique activity functions both in a translational quality control mechanism and in regulation of gene expression, tmRNA is conserved throughout the bacterial kingdom, and is required for processes such as pathogenesis, symbiosis, stress tolerance, and bacterial development. The long-term objective of this application is to understand the mechanism of action and physiological role of tmRNA in bacteria. This application focuses on the role of tmRNA in the development and cell cycle regulation of Caulobacter crescentus. C. crescentus is the organism of choice for these studies because the extensive knowledge of the molecular events that control its cell cycle and developmental program provide a unique opportunity to determine the influence of tmRNA activity on cellular differentiation and DNA replication, tmRNA is required for proper timing of DNA replication and the coincident differentiation from swarmer cell to stalked cell in C. crescentus. The primary goals of this application are: to identify substrates for tmRNA in C. crescentus that are important for control of DNA replication, to determine how tmRNA activity on these substrates affects DNA replication, and to understand how the activity of tmRNA is controlled by the genetic regulatory network of the cell.

描述（由申请人提供）：通过非编码 RNA (ncRNA) 调节基因表达是生物学中的新兴范例。 ncRNA 在从噬菌体到人类的多种生物体中调节多种过程，包括转录、翻译、RNA 修饰、mRNA 稳定性、RNA 剪接、染色质结构以及蛋白质稳定性和活性。真核和原核基因组包含数百个未表征的 ncRNA，这些基因越来越多地被确定为导致发育缺陷和多种人类疾病的突变位点。 这些 ncRNA 中最有趣的一个是 tmRNA，这是一种兼具 tRNA 和 mRNA 特性的分子，它会干预选定的翻译反应。 tmRNA 识别选定的翻译复合物并进入核糖体，介导向新生多肽添加肽标签，靶向蛋白质快速降解并释放核糖体和 mRNA。这种独特的活性在翻译质量控制机制和基因表达调节中发挥作用，tmRNA 在整个细菌界中都是保守的，并且是发病机制、共生、应激耐受和细菌发育等过程所必需的。该应用的长期目标是了解细菌中 tmRNA 的作用机制和生理作用。 本申请重点关注 tmRNA 在新月柄杆菌发育和细胞周期调节中的作用。 C. crescentus 是这些研究的首选生物体，因为对控制其细胞周期和发育程序的分子事件的广泛了解为确定 tmRNA 活性对细胞分化和 DNA 复制的影响提供了独特的机会，tmRNA 是 DNA 复制的正确定时以及 C. crescentus 中从群细胞到茎细胞的同步分化所必需的。该应用的主要目标是：鉴定 C. crescentus 中对控制 DNA 复制很重要的 tmRNA 底物，确定这些底物上的 tmRNA 活性如何影响 DNA 复制，并了解 tmRNA 的活性如何受细胞的遗传调控网络控制。