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调节从噬菌体到人类的多种生物体中的多种过程，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。真核生物和原核生物的基因组中含有数百个未被鉴定的ncRNA，这些基因越来越多地被鉴定为导致发育缺陷和多种人类疾病的突变位点。 这些ncRNA中最令人感兴趣的是tmRNA，一种具有tRNA和mRNA性质的分子，其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以介导向新生多肽添加肽标签，靶向蛋白质以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控中发挥作用，tmRNA在整个细菌界是保守的，并且是致病、共生、胁迫耐受和细菌发育等过程所必需的。本申请的长期目标是了解细菌中tmRNA的作用机制和生理作用。 本申请的重点是tmRNA在新月柄杆菌的发育和细胞周期调控中的作用。C. crescentus是这些研究的首选生物体，因为控制其细胞周期和发育程序的分子事件的广泛知识提供了一个独特的机会来确定tmRNA活性对细胞分化和DNA复制的影响，tmRNA是正确的DNA复制时间和C中的群集细胞向柄细胞的同步分化所必需的。crescentus。本申请的主要目的是：鉴定C. crescentus，是重要的控制DNA复制，以确定如何在这些基板上的tmRNA的活动影响DNA复制，并了解如何通过细胞的遗传调控网络控制的tmRNA的活动。