细菌信使RNA非翻译区衍生小RNA的生物学功能研究

Similar function as miRNA or lncRNA in eukaryote, small non-coding RNAs (sRNAs) have been recognized as a major class of crucial regulatory molecules in prokaryote. It regulate the targets mRNA via base-paring in the post-transcriptional level. It has been assumed that the vast majority of sRNAs are encoded by conserved free-standing genes with independent promoters and transcription start/terminal sites. However, recently study and our preliminary results have proved that in Salmonella typhimurium, a plethora of new small RNA species are encoded within mRNA loci, in particular from the un-translated region of protein-coding genes. Several of these are generated by the processing of mRNA transcripts and might have important biological role, as implied by their conserved sequences and secondary structures. Based on these data, we hypothesize that bacterial mRNA may serve as a precursor for generating sRNAs to regulate related biological process. In this project, we will study 2 sRNAs that are generated through mRNA processing in Salmonella typhimurium. We will characterize the molecular mechanism of sRNA biogenesis and the functional characterization of targets of selected cleavage derived sRNAs. We will also elucidate the physiological meaning of the dual functions (protein synthesis and sRNAs biogenesis) of coding genes that generate both an mRNA and sRNA. These studies will provide novel insights into a previously uncharacterized aspect of bacterial gene regulation.

与真核生物miRNA等具有调控作用的非编码RNA类似，原核生物非编码小RNA(sRNA)也可以在转录后水平调控靶基因的表达，从而在许多生物学过程中发挥重要作用。传统观点认为sRNA是独立编码和转录的基因，有独立的启动子、转录起始和终止位点。新近研究和我们前期结果却发现，鼠伤寒沙门氏菌中一些sRNA可以通过RNA酶剪切的方式从mRNA的非翻译区衍生出。分析这些sRNA的序列发现它们具有保守的序列和二级结构，提示其可能有重要的生物学功能。因此，我们提出细菌mRNA可以通过RNA酶剪切衍生出sRNA来调控相关生物学过程的科学假设。本课题将选取两个鼠伤寒沙门氏菌mRNA衍生出的sRNA，使用RNA分子生物学等研究手段，结合RNA测序技术，研究sRNA衍生的分子机制、生物学功能、与母体基因生物学功能的联系等。本课题的研究成果不仅可以阐明所选取sRNA的生物学功能，而且将丰富对细菌mRNA功能的认识。