Nuclear Actin in Transcription

肌动蛋白和肌球蛋白是细胞质蛋白质，它们在肌肉收缩中的作用是众所周知的，它们参与了细胞核中DNA转录成RNA的过程，这种说法几乎是异端。然而，在细胞核中发现了一种称为核肌球蛋白I的肌球蛋白。肌动蛋白在细胞核中也很丰富。重要的是，已经确定肌动蛋白和核肌球蛋白I在转录中是重要的。 然而，这些蛋白质如何参与转录的细节尚不清楚。因此，本计画将探讨肌动蛋白参与转录的多个阶段。有两个具体目标。具体目标1将探讨肌动蛋白是如何参与前起始复合物（PIC）的形成。PIC的形成是转录的第一步，涉及到一系列蛋白质在基因启动子区的结合。尽管肌动蛋白对于PIC的形成是必需的，但它何时以及如何被招募到发育中的PIC中，但它与哪些蛋白质相关以及它在PIC中是否具有酶或结构功能尚不清楚。这些问题是具体目标1的主题。具体目标2将研究参与转录的肌动蛋白的形式。肌动蛋白可以单体形式存在，也可以聚合形成长纤维（F-肌动蛋白）。F-肌动蛋白是参与肌肉收缩的肌动蛋白的形式。然而，肌动蛋白丝从来没有被证明在细胞核中。因此，一个核心问题，关于肌动蛋白在细胞核中是核过程是否需要单体或丝状肌动蛋白。这一问题将在具体目标2中处理。这些数据可能会改变我们对转录的理解，这是一个对我们所知的生命至关重要的过程。此外，这项研究将有助于美国和国际本科生、研究生和博士后研究员的教育。它还将促进与美国和欧洲调查人员的合作。该项目由Genes and Genome Systems and Cellular Systems共同资助。

The suggestion that actin and myosin, cytoplasmic proteins best known for their role in muscle contraction, are involved in the transcription of DNA into RNA in the nucleus is almost heretical. Nevertheless, a type of myosin, called nuclear myosin I, has been identified in the nucleus. Actin is also abundant in the nucleus. Importantly, it has been established that actin and nuclear myosin I are important in transcription. However, the details of how these proteins are involved in transcription are not known. Therefore, this project will investigate the proposition that actin is involved in multiple stages of transcription. There are two specific aims. Specific aim 1 will investigate how actin is involved in pre-initiation complex (PIC) formation. PIC formation is the first step in transcription and involves the association of a host of proteins at the promoter region of a gene. Although actin is necessary for PIC formation, when and how it is recruited to the developing PIC, what proteins it associates with and whether it has an enzymatic or structural function in the PIC is not known. These questions are the subject of specific aim 1. Specific aim 2 will investigate the form of actin that is involved in transcription. Actin can exist as a monomer or it can polymerize to form long filaments (F-actin). F-actin is the form of actin involved in muscle contraction. However, actin filaments have never been demonstrated in the nucleus. Therefore, a central question regarding actin in the nucleus is whether nuclear processes require monomeric or filamentous actin. This question will be addressed in specific aim 2. Data from these could potentially change our understanding of transcription, a process that is fundamental to life as we know it. In addition, this research will contribute to the education of American and international undergraduate and graduate students and post-doctoral fellows. It will also promote collaborations with American and European investigators. This project is co-funded through Genes and Genome Systems and Cellular Systems.