CONTROL OF TRANSCRIPTION IN EUKARYOTIC CELLS

为了全面了解真核生物中基因表达的调控， 细胞，这是必要的，以实现更大的了解RNA 合成机制，这是最重要的目标之一， 调控途径。 现在已知RNA聚合酶II， 合成所有蛋白质编码RNA，在许多方面受到控制， 点：在起始复合物的组装处。在过渡到 在伸长过程中在不连续的阻滞部位。我们 长期目标是为两个基本问题提供答案：第一， 伴随RNA转变的分子事件是什么 聚合酶II从不稳定的起始状态到稳定的延伸 第二，RNA聚合酶II的延伸发生了什么变化， 复合体负责在生长过程中丧失伸长能力， 逮捕？为了让RNA聚合酶成功地从 前起始复合物稳定转录延长，它必须逃脱 一个失败的起始途径并开始沿着模板易位。 将采用简化的转录起始系统来研究 流产成功逃逸的顺序和因素要求 入会仪式我们还将对以下结构参数进行比较： 一系列的复合物， 为了确定伴随经济转型的结构性变化， 转化为延伸能力。类似的一系列实验是 建议研究伴随着丧失能力的过渡， 在逮捕期间延长;在这种情况下，我们希望确定结构 被逮捕国家的特征。为了配合后一项研究， 我们将尝试更全面地定义导致 逮捕了我们还将把早期的研究扩展到分子机制， 为了更好地理解记录， 裂解/再合成反应，这是回收所需的。

In order to fully understand the control of gene expression in eukaryotic cells, it is necessary to achieve a much greater understanding of the RNA synthesis machinery, which is one of the most important targets for regulatory pathways. It is now known that RNA polymerase Il, which synthesizes all protein-encoding RNAs, is subject to control at many points: at the assembly of the initiation complex. at the transition into elongation and at discrete arrest sites during the elongation process. Our long-term goal is to provide answers to two fundamental questions: first, what are the molecular events that accompany the transition of RNA polymerase II from the unstable, initiating state to the stable elongation state, and second, what changes in the RNA polymerase II elongation complex are responsible for the loss of elongation competence during arrest? In order for the RNA polymerase to successfully pass from the preinitiation complex to stable transcript elongation, it must escape from an abortive initiation pathway and begin translocation down the template. Simplified systems for transcription initiation will be employed to study the sequence and factor requirements for successful escape from abortive initiation. We will also make a comparison of structural parameters among a series of complexes which are passing through the initiation-elongation transition, in order to identify structural changes which accompany the conversion to elongation competence. A similar series of experiments are proposed to study the transitions that accompany loss of the ability to elongate during arrest; in this case we hope to identify structural features distinctive to the arrested state. To accompany this latter study we will attempt to define more fully the sequence signals that cause arrest. We will also extend earlier studies into the molecular mechanisms of recovery from arrest, in order to better understand the transcript cleavage/resynthesis reaction which is required for recovery.