Belogurov Georgiy A, Mooney Rachel A, Svetlov Vladimir, Landick Robert, Artsimovitch Irina
Department of Microbiology and The RNA Group, The Ohio State University, Columbus, OH 43210, USA.
EMBO J. 2009 Jan 21;28(2):112-22. doi: 10.1038/emboj.2008.268. Epub 2008 Dec 18.
Elongation factors NusG and RfaH evolved from a common ancestor and utilize the same binding site on RNA polymerase (RNAP) to modulate transcription. However, although NusG associates with RNAP transcribing most Escherichia coli genes, RfaH regulates just a few operons containing ops, a DNA sequence that mediates RfaH recruitment. Here, we describe the mechanism by which this specificity is maintained. We observe that RfaH action is indeed restricted to those several operons that are devoid of NusG in vivo. We also show that RfaH and NusG compete for their effects on transcript elongation and termination in vitro. Our data argue that RfaH recognizes its DNA target even in the presence of NusG. Once recruited, RfaH remains stably associated with RNAP, thereby precluding NusG binding. We envision a pathway by which a specialized regulator has evolved in the background of its ubiquitous paralogue. We propose that RfaH and NusG may have opposite regulatory functions: although NusG appears to function in concert with Rho, RfaH inhibits Rho action and activates the expression of poorly translated, frequently foreign genes.
延伸因子NusG和RfaH起源于一个共同祖先，并利用RNA聚合酶（RNAP）上的相同结合位点来调节转录。然而，尽管NusG与转录大多数大肠杆菌基因的RNAP相关联，但RfaH仅调节少数含有ops的操纵子，ops是一种介导RfaH募集的DNA序列。在这里，我们描述了维持这种特异性的机制。我们观察到，RfaH的作用确实仅限于体内缺乏NusG的那几个操纵子。我们还表明，RfaH和NusG在体外对转录延伸和终止的影响上相互竞争。我们的数据表明，即使在存在NusG的情况下，RfaH也能识别其DNA靶标。一旦被募集，RfaH就会与RNAP稳定结合，从而阻止NusG的结合。我们设想了一条在其普遍存在的旁系同源物背景下进化出一种特殊调节因子的途径。我们提出，RfaH和NusG可能具有相反的调节功能：尽管NusG似乎与Rho协同发挥作用，但RfaH抑制Rho的作用并激活翻译效率低、通常为外源基因的表达。
