Prokaryotic RNA Metabolism

这些研究将集中于使用分子生物学、生化和遗传学方法来阐明信使RNA在细菌中是如何降解的。RppH是最近发现的一种RNA焦磷水解酶，它通过一种以前未知的机制触发大肠杆菌初级转录本的降解：决定5‘端三磷酸转化为一磷酸的速率。首先，将确定RNA的特征，这些特征决定了它们通过这种机制对衰退的敏感性。此外，还将研究对其活性重要的RppH的特征，以及可能影响这种5‘端依赖的RNA降解的细胞因素。最后，这一途径对其他细菌物种的mRNA衰退的贡献将被探索。这些研究的结果将为目前知之甚少的基因调控的一个基本方面提供重要的见解。这一知识对阐明在细菌发病机制中发挥关键作用的生物调节机制应该是有价值的。

These investigations will focus on using molecular biological, biochemical, and genetic methods to elucidate how messenger RNA is degraded in bacteria. Particular attention will be devoted to RppH, a recently discovered RNA pyrophosphohydrolase that triggers the degradation of primary transcripts in E. coli by a previously unrecognized mechanism: the rate-determining conversion of the 5'-terminal triphosphate to a monophosphate. First, the features of RNAs that determine their susceptibility to decay by this mechanism will be identified. In addition, the characteristics of RppH that are important for its activity and the cellular factors that may influence such 5'-end- dependent RNA degradation will be examined. Finally, the contribution of this pathway to mRNA decay in other bacterial species will be explored. The results of these studies will provide important insights into a fundamental aspect of gene regulation that presently is poorly understood. This knowledge should be of value in clarifying a biological regulatory mechanism that can play a key role in bacterial pathogenesis.