The role of tmRNA in development of C. crescentus

描述(由申请人提供)：通过非编码RNA(NcRNAs)调节基因表达是生物学中的一个新兴范例。在从噬菌体到人类的各种生物体中，ncRNAs调控着一系列的过程，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的稳定性和活性。真核和原核基因组包含数百个未鉴定的ncRNA，这些基因越来越多地被认为是导致发育缺陷和几种人类疾病的突变基因。 这些ncRNAs中最有趣的一个是tmRNA，这是一种同时具有tRNA和mRNA性质的分子，它参与选定的翻译反应；tmRNA识别选定的翻译复合体，进入核糖体，介导将肽标签添加到新生多肽中，针对蛋白质进行快速降解并释放核糖体和mRNA。这种独特的活性既在翻译质量控制机制中发挥作用，也在基因表达调控中发挥作用，tmRNA在整个细菌界中都是保守的，是致病、共生、胁迫耐受和细菌发育等过程所必需的。这一应用的长期目标是了解tmRNA在细菌中的作用机制和生理作用。 本文重点介绍了tmRNA在新月弯杆菌生长发育和细胞周期调控中的作用。Crescentus是这些研究的首选生物，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复制的适当时机和从沼泽细胞到柄细胞的一致分化所必需的。这一应用的主要目标是：确定crescentus中tmRNA的底物，确定这些底物上的tmRNA活性如何影响DNA复制，以及了解tmRNA的活性如何受细胞的遗传调控网络控制。

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.