Nuclear Actin in Transcription

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

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.