The study of non-canonical transcriptions systems in bacteria

在所有生命形式中，一种称为RNA聚合酶的酶复合物负责细胞中基因的表达。在细菌中，这种复合物本身不能与DNA结合，它需要另一种称为sigma因子的酶亚基。σ因子结合RNA聚合酶，形成所谓的全酶，全酶能够结合每个基因的启动子区域并激活基因表达。每个细菌物种编码一个或多个σ因子，共同确保细胞中所有基因的协调表达。我们的实验室研究sigma因子的分子功能，包括在某些物种中发现的这种蛋白质的不寻常形式。最近，我们在枯草芽孢杆菌中发现了一种不寻常的sigma因子。这种sigma因子由两种单独的蛋白质组成，称为YvrI和YvrHa，这些酶一起催化通常由holoenzme中的单一蛋白质sigma因子完成的事情。我们的研究计划提出了一系列项目，将有助于解释这种不寻常的双亚基sigma因子如何与RNA聚合酶相互作用，以及由此产生的全酶如何识别和结合DNA以激活基因表达。我们也在研究基于YvrI-YvrHa的全酶的DNA结合位点。了解基因如何在细菌中表达对于理解生命的分子本质以及工业和医学中的许多追求（包括发现新抗生素）都很重要。

In all life-forms, an enzyme complex called RNA polymerase is responsible for the expression of genes in cells. In bacteria, this complex itself cannot bind to DNA and it requires another enzyme subunit called sigma factor. Sigma factors bind RNA polymerase forming what is called holoenzyme and holoenzyme is capable of binding the promoter region of each gene and activating gene expression. Each bacterial species encodes one or more sigma factors that together ensure the coordinated expression of all genes in the cell. Our lab studies the molecular function of sigma factors including unusual forms of this protein found in some species. Recently, we discovered an unusual form of sigma factor in the model bacterium Bacillus subtilis. This sigma factor is composed of two individual proteins called YvrI and YvrHa and these enzymes work together to catalyze what is usually accomplished by a single protein sigma factor in holoenyzme. Our research plan proposes a series of projects that will help explain how this unusual two-subunit sigma factor interacts with RNA polymerase, and how the resulting holoenzyme recognizes and binds DNA to activate gene expression. We are also examining the DNA-binding site for YvrI-YvrHa based holoenzyme. Understanding how genes are expressed in bacteria is important for understanding the molecular nature of life and for many pursuits in industry and medicine including the discovery of new antibiotics.