项目组前期研究发现金黄色葡萄球菌小RNA SprC与转录调节子iraC mRNA结合下调其翻译并致杀白细胞素lukED转录抑制，但机制不明。IraC为AraC家族蛋白，具有与靶基因启动子区结合调控转录的特点。细菌sRNA主要通过结合mRNA核糖体结合位点（RBS）影响靶蛋白翻译，RNA伴侣Hfq能促进两者结合，结合后可能触发RNase III活性影响mRNA稳定性。故推测：SprC下调IraC表达可能是通过结合iraC mRNA RBS实现的；Hfq和RNase III可能促进两者结合及降低mRNA的稳定性；IraC表达下降导致其与lukED结合减少，从而解除IraC对lukED的转录调控。本项目拟阐明SprC下调IraC并致lukED转录抑制的分子机制，探讨Hfq及RNase III对该调控网络的影响。研究结果有助于深入了解金黄色葡萄球菌致病机理，为改进该菌感染的预防和治疗策略提供线索。

It was shown by our group that small RNA SprC of Staphylococcus aureus (S. aureus) down-regulates the expression of transcriptional regulator IraC by binding to iraC mRNA, and further inhibits the transcription of leukotoxin ED (lukED) gene. However the mechanisms of this regulatory network are unknown. IraC is a member of AraC family proteins, which are able to regulate genes transcription by directly binding the promoter region of target genes. Previous studies have shown that most of bacterial sRNAs regulate the proteins expression in translation level by binding to the ribosome-binding site (RBS) of the target mRNA; the RNA chaperone Hfq can promote the duplex formation between sRNA and target mRNA, and this binding may trigger the activity of RNase III affecting the stability of target mRNA. Therefore, we speculate that SprC down-regulates the expression of IraC by combining with the RBS of iraC mRNA; Hfq may promote the binding of SprC-iraC mRNA, and RNase III may reduce the stability of target mRNA in complex, which futher leads to the decrease of IraC expression; The down-regulation of the expression of IraC results in the reduction of this protein combining with the lukED, and the regulatory role of IraC on the transcription of lukED will be relieved. In this research project we will elucidate the molecular mechanisms of inhibition of lukED expression by SprC via down-regulation of transcriptional regulator IraC, and explore the roles of Hfq and RNase III in this regulatory network. This study will help us deeply understand the pathogenesis of S. aureus, and give a clue for improving the prevention and therapy strategies of S. aureus infections.