Nuclear Actin in Transcription

肌动蛋白和肌凝蛋白这两种细胞质蛋白以其在肌肉收缩中的作用最为人所知，它们参与了细胞核中DNA转录为RNA的过程，这种说法几乎是异端邪说。然而，在细胞核中发现了一种称为核肌球蛋白I的肌凝蛋白。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在转录中起重要作用。然而，这些蛋白质如何参与转录的细节尚不清楚。因此，本项目将研究肌动蛋白参与多个转录阶段的命题。有两个具体目标。具体目标1将研究肌动蛋白如何参与起始前复合物（PIC）的形成。PIC的形成是转录的第一步，涉及在基因启动子区域的一系列蛋白质的结合。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正在发育的PIC中，它与什么蛋白质相关，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。肌动蛋白可以作为单体存在，也可以聚合形成长丝（f -肌动蛋白）。肌动蛋白是参与肌肉收缩的一种肌动蛋白。然而，肌动蛋白丝从未在细胞核中被证实。因此，关于核中肌动蛋白的一个核心问题是核过程是需要单体肌动蛋白还是丝状肌动蛋白。这个问题将在具体目标2中讨论。这些数据可能会改变我们对转录的理解，而转录是我们所知的生命的基础。此外，本研究将有助于美国和国际本科生、研究生和博士后的教育。它还将促进与美国和欧洲研究人员的合作。该项目由基因与基因组系统和细胞系统共同资助。

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.