Sun Wei-Sheng W, Chen Jenn-Wei, Wu Yi-Chih, Tsai Hsing-Yuan, Kuo Yu-Liang, Syu Wan-Jr
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
Taiwan International Graduate Program in Molecular Medicine, Academia Sinica, Taipei, Taiwan, R.O.C.
PLoS One. 2016 May 16;11(5):e0155578. doi: 10.1371/journal.pone.0155578. eCollection 2016.
Enterohaemorrhagic Escherichia coli O157:H7 (EHEC) carries a pathogenic island LEE that is consisted mainly of five polycistronic operons. In the lee3 operon, mpc is the first gene and has been reported to down regulate the type-3 secretion system of EHEC when its gene product is over-expressed. Furthermore, mpc has been suggested to have a regulation function via translation but the mechanism remains unclear. To clarify this hypothesis, we dissected the polycistron and examined the translated products. We conclude that translation of mpc detrimentally governs the translation of the second gene, escV, which in turn affects the translation of the third gene, escN. Then sequentially, escN affects the expression of the downstream genes. Furthermore, we located a critical cis element within the mpc open-reading frame that plays a negative role in the translation-dependent regulation of lee3. Using qRT-PCR, we found that the amount of mpc RNA transcript present in EHEC was relatively limited when compared to any other genes within lee3. Taken together, when the transcription of LEE is activated, expression of mpc is tightly controlled by a restriction of the RNA transcript of mpc, translation of which is then critical for the efficient production of the operon's downstream gene products.
肠出血性大肠杆菌O157:H7(EHEC)携带一个致病岛LEE,该致病岛主要由五个多顺反子操纵子组成。在lee3操纵子中,mpc是第一个基因,据报道,当其基因产物过度表达时,mpc会下调EHEC的Ⅲ型分泌系统。此外,有人提出mpc通过翻译发挥调控作用,但其机制尚不清楚。为了阐明这一假设,我们剖析了多顺反子并检测了翻译产物。我们得出结论,mpc的翻译对第二个基因escV的翻译产生不利影响,进而影响第三个基因escN的翻译。然后依次地,escN影响下游基因的表达。此外,我们在mpc开放阅读框内定位了一个关键的顺式元件,该元件在lee3的翻译依赖性调控中起负性作用。使用qRT-PCR,我们发现与lee3内的任何其他基因相比,EHEC中存在的mpc RNA转录本数量相对有限。综上所述,当LEE的转录被激活时,mpc的表达通过对mpc RNA转录本的限制而受到严格控制,其翻译对于操纵子下游基因产物的有效产生至关重要。