The alpha subunits of Francisella tularensis RNA polymerase

描述（由申请人提供）：土拉菌弗朗西斯菌是土拉菌病的病原，是目前已知最具传染性的细菌病原体之一，也是潜在的生物武器。它既是一种环境生物，也是一种病原体，因此必须在各种不同的条件下生存。然而，引人注目的是，土拉菌编码的转录调控因子相对较少。对土拉菌基因组序列的检测发现，两个基因分别编码RNA聚合酶（RNAP）的a亚基，分别为rpoA1和rpoA2。这种情况是史无前例的；在迄今为止测序的所有其他细菌基因组中只有一个rpoA基因。由于a通过直接序列特异性蛋白质- dna相互作用参与启动子识别，并且a是转录激活子的共同靶标，因此在a含量方面彼此不同的RNAP分子可能具有非常不同的性质。在这里，我们建议采用遗传和生化方法相结合的方法来确定土拉菌的RNAP是否包含两个功能不同的a亚基。这些研究将对如何控制土拉菌的基因表达具有重要意义；使用具有不同a亚基的RNAP群体可能代表了识别不同类型启动子和控制转录的独特策略，可能在设计特异性靶向土拉菌的抗菌剂中被利用。

DESCRIPTION (provided by applicant): Francisella tularensis, the aetiological agent of tularemia, is one of the most infectious bacterial pathogens currently known and a potential biological weapon. It is both an environmental organism and a pathogen, and must therefore survive under widely varying conditions. Strikingly, however, F. tularensis encodes relatively few transcription regulators. Inspection of the F. tularensis genome sequence reveals two genes, designated rpoA1 and rpoA2, encoding different a subunits of RNA polymerase (RNAP). This situation is without precedent; in all other bacterial genomes sequenced to date there is only one rpoA gene. Because a participates in promoter recognition through direct sequence-specific protein-DNA interactions, and because a is a common target for transcription activators, RNAP molecules that differ from one another with respect to their a content may have very different properties. Here we propose to take a combination of genetic and biochemical approaches to determine whether or not RNAP in F. tularensis contains two functionally distinct a subunits. These studies will have important implications for how gene expression is controlled in F. tularensis; the use of an RNAP population with different a subunits may represent a unique strategy for recognizing different classes of promoter and controlling transcription, one that might be exploited in the design of antimicrobials that specifically target F. tularensis.