陈士云研究组最新文章解析小RNA调控机制

　　

　小RNA(Small non-coding RNA, sRNA)是细菌重要的转录后调控因子，广泛参与调控细菌各方面的功能。由于不同sRNA调控的靶标及其调控机制不相同，多数已鉴定sRNA 的靶基因未知，且一些已知靶基因的sRNA 是否存在新的调控靶标及调控机制也不清楚，因此sRNA一直是原核生物调控型RNA研究的热点。

　　近期，中国科学院武汉病毒研究所研究员陈士云带领的病原细菌学科组在sRNA功能及调控机制研究方面取得进展。该研究以临床重要的机会致病菌——铜绿假单胞菌为对象，通过生物信息学等方法鉴定出依赖于细菌压力耐受因子RpoS的sRNA—RgsA的2个调控靶标：酰基转运蛋白AcpP及全局性调控蛋白Fis；在伴侣蛋白Hfq的辅助下，RgsA通过不完全互补配对方式调控这2个靶标的表达。进一步研究发现，fis mRNA有两个起始密码子，且均受到RgsA的调控，并找到了调控的关键区域。RgsA还通过抑制细菌生长、运动性及促进毒素的分泌，参与调控细菌的毒力及生长等表型。该研究首次将全局性转录调控因子Fis与压力相关因子RpoS通过sRNA的调控联系起来，揭示了细菌在应对外界环境信号及压力条件时，RgsA反馈调控AcpP和Fis这2个靶标的具体机制。

　　该研究由助理研究员卢培等人完成，论文在线发表在《分子微生物学》（Molecular Microbiology）。该研究得到国家自然科学基金青年基金项目（#31300124）的资助。

RgsA 通过反义互补配对直接调控fis及acpP表达

原文摘要：

RpoS-dependent sRNA RgsA regulates Fis and AcpP in Pseudomonas aeruginosa

RgsA is a phylogenetically conserved small regulatory RNA (sRNA) in Pseudomonas species. This sRNA has been shown to be directly controlled by the major stationary phase and stress sigma factor σS (RpoS), and also indirectly regulated by the GacS/GacA two-component system. However, the role and the regulatory targets of this sRNA remain unclear. Here, two direct regulatory targets of RgsA, the mRNAs coding for the global transcriptional regulator Fis and the acyl carrier protein AcpP, were identified in P. aeruginosa. RgsA downregulates the synthesis of Fis and AcpP by base-pairing, and this regulation requires the RNA chaperone protein Hfq. Alignment of RgsA homologs in Pseudomonas revealed a conserved core region, which is strictly required for RgsA target recognition. Specifically, RgsA inhibits fis expression via an 11 + 11 bp RNA duplex, whereas this interaction region is not sufficient for repression and the 35 nt downstream region is also required. Interestingly, two functional start codons initiate fis mRNA translation and both are repressed by RgsA. Furthermore, deletion of rgsA significantly increased swarming motility in P. aeruginosa. Together, this study suggests a novel regulatory role of sRNA in which the versatile transcriptional regulator Fis and the stress regulator RpoS are connected by RgsA.