Exploring biogenesis and functions of 3'UTR-derived small regulatory RNAs

大多数对小调控rna （sRNAs）的研究都集中在细菌染色体基因间区非编码基因的转录本上。然而，越来越多的证据表明，mRNA基因的3-prime区域构成了一个新的sRNAs进化的额外的大库。迄今为止，这类3-prime utr衍生的sRNAs在功能方面的研究很少，这类新兴细菌核糖体调节剂的生物发生原理和细胞靶点的调控仍有待阐明。在这个项目中，我们将关注通过mRNA加工产生的3-prime utr衍生的sRNAs，并询问这些sRNAs是否与其亲本mRNA中的蛋白质在相同的途径中起作用。为此，我们选择了两个有希望的候选基因，CpxQ和RybD，它们分别在包膜胁迫控制和代谢调节中发挥预测作用。这两种3- ' utr衍生的sRNAs都是保守的，与Hfq蛋白相关，并显示出条件依赖功能的表达；一种是由细菌Cpx应激途径中重要伴侣的单顺反子mRNA组成，另一种是由重要代谢酶的长操纵子mRNA组成。这两种sRNAs中的每一种都有其他吸引人的原因：CpxQ可能是保守的cpxr介导的应激反应中缺失的一环，该应激反应正在成为新的药物靶点；RybD可能是迄今为止已知的最短的功能性hfq相关sRNA，可以作为高分辨率结构分析的模型。更一般地说，了解这些3- ' utr衍生的sRNAs的细胞作用将有助于深入了解为什么在某些情况下细胞更倾向于调节性RNA分子而不是调节性蛋白质。

Most investigations of small regulatory RNAs (sRNAs) have focused on transcripts from noncoding genes in the intergenic regions of bacterial chromosomes. However, there is growing evidence to suggest that the 3-prime regions of mRNA genes constitute an additional large reservoir from which new sRNAs evolve. To date, very few such 3-prime UTR-derived sRNAs have been investigated with respect to function, and both the biogenesis principles and regulation of the cellular targets of this emerging class of bacterial riboregulators remain to be elucidated. In this project we will focus on 3-prime UTR-derived sRNAs that are generated through mRNA processing and ask if such sRNAs function in the same pathway as the proteins from their parental mRNAs. To this end, we have selected two promising candidates, CpxQ and RybD, with predicted roles in envelope stress control and metabolic regulation, respectively. Both these 3-prime UTR-derived sRNAs are well-conserved, associate with Hfq protein, and show expression indicative of a condition-dependent function; one is made from a monocistronic mRNA of an important chaperone in the bacterial Cpx stress pathway, the other from the long operon mRNA of important metabolic enzymes. Each of these two sRNAs is attractive for additional reasons: CpxQ may be a missing link in the conserved CpxR-mediated stress response that is emerging as a new drug target; RybD may be the shortest functional Hfq-associated sRNA known to date and lends itself as a model for high-resolution structural analysis. More generally, understanding the cellular roles of these 3-prime UTR-derived sRNAs will provide insight into the fundamental question why in some situations cells favour regulatory RNA molecules over regulatory proteins.