The role of tmRNA in development of C. crescentus

tmRNA 在 C. crescentus 发育中的作用

• 批准号: 6778409
• 负责人: KENNETH C KEILER
• 金额: $ 22.89万
• 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/6778409
• 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）：非编码RNA（NCRNA）对基因表达的调节是生物学的新兴范式。 NCRNA调节各种过程，包括从噬菌体到人类的各种生物体中的各种生物，包括转录，翻译，MRNA稳定性，RNA剪接，染色质结构以及蛋白质稳定性以及活性。真核和原核生物基因组含有数百种未表征的NCRNA，并且这些基因越来越被鉴定为引起发育缺陷和几种人类疾病的突变的基因座。 这些NCRNA中最有趣的是TMRNA，TMRNA是具有tRNA和mRNA的特性的分子，它介入了选定的翻译反应中。 TMRNA识别选定的翻译复合物并进入核糖体以介导向新生的多肽添加肽标签，靶向蛋白质以快速降解并释放核糖体和mRNA。这种独特的活性在转化质量控制机制和基因表达的调节中都起着作用，在整个细菌界都保守了TMRNA，并且是发病机理，共生，胁迫耐受性和细菌发育等过程所必需的。该应用的长期目标是了解TMRNA在细菌中的作用机理和生理作用。 该应用的重点是TMRNA在Caulobacter Crescentus的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，因为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需要适当的DNA复制时间来进行DNA复制时间，并且从swarmer c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. crosentecents c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. c. cinterniation。所必需的。 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.