Structure and function of the archaeal transcription factor C34/TFEbeta: The structural and functional characterisation of an archaeal homologue of the general transcription factor TFIIEbeta and the RNA polymerase III subunit C34 will provide insight into

地球上细胞生命早期演化的一个重大事件是它分成了三个领域，在细胞的结构和功能组织上存在根本的差异：细菌、古生菌和真核生物(酵母、植物、动物等)。在所有的细胞生命中，RNA聚合酶是蛋白质复合体，负责基因表达的第一步，即DNA到RNA的转录。在真核生物中，不同类型的RNA聚合酶转录不同类别的基因。每种不同类型的RNA聚合酶都被一组特定的转录启动因子蛋白招募到其靶基因上。古生菌和细菌对所有基因都使用单一的RNA聚合酶。值得注意的是，古生菌RNA聚合酶及其通用转录因子类似于真核RNA聚合酶II和III，它们具有基本的通用转录因子集。因此，对古生代转录的研究为转录过程以及它如何在进化过程中保持保守提供了基本的见解。我最近发现了与真核细胞TFIIEbeta和C34相对应的古生菌蛋白，这两种蛋白分别参与真核RNA聚合酶II和III的转录启动。古生菌C34/TFEbeta在古生菌和真核生物转录机制的进化史上代表着一个“缺失的环节”。该项目研究了古生菌C34/TFEbeta的生物学功能，特别是其在转录启动中的作用。此外，我还将确定古生菌C34/TFEbeta蛋白与转录装置的其他组件形成的相互作用网络。总的目标是揭示古生菌C34/TFEbeta蛋白与其真核对应蛋白之间的结构和功能同源性。这项拟议的项目将促进我们对古生物和真核生物中RNA聚合酶和转录系统早期进化的理解。

A major event in the early evolution of cellular life on Earth has been its branching into three domains with fundamental differences concerning the structural and functional organization of cells: Bacteria, Archaea and Eukaryotes (yeast, plants, animals etc.). In all cellular life, RNA polymerases are protein complexes responsible for the first step in gene expression, the transcription of DNA to RNA. In Eukaryotes, different types of RNA polymerases transcribe different classes of genes. Each of the different types of RNA polymerases is recruited to its target genes by a specific set of transcription inititiation factor proteins. Archaea and Bacteria use a single RNA polymerase for all genes. Notably, the archaeal RNA polymerase and its general transcription factors resemble the eukaryotic RNA polymerases II and III with their basic sets of general transcription factors. Studies on transcription in Archaea have therefore provided fundamental insight on the process of transcription and how it remained conserved during the course of evolution. I have recently identified the archaeal protein that forms the counterpart to eukaryotic TFIIEbeta and C34, two related proteins with functions in transcription initiation of eukaryotic RNA polymerases II and III, respectively. The archaeal C34/TFEbeta represents a „missing link“ in the evolutionary history of archaeal and eukaryotic transcription machineries. The proposed project investigates the biological function of archaeal C34/TFEbeta, especially its role in transcription initiation. In addition, I will determine the interaction network that the archaeal C34/TFEbeta protein forms with other components of the transcription apparatus. The overall goal is to reveal structural and functional homologies between the archaeal C34/TFEbeta protein and its eukaryotic counterparts. The proposed project will advance our understanding of the early evolution of RNA polymerases and transcription systems in Archaea and Eukaryotes.