Protein Arginine Methylation by PRMT1

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).In order to increase the functionality of the small number of proteins encoded by mammalian genomes, proteins are often decorated with a variety of chemical appendages that alter the behavior of the protein. Having the ability to alter proteins in this way is a hallmark feature of any cell's ability to adapt its response to the environment. In the first aim, this project will use novel methods and mechanistic approaches to clarify how one of these enzymes, called protein arginine methyltransferase 1 (PRMT1), recognizes its target proteins and how it performs the chemical transformation (protein arginine methylation). In particular the project will study a novel regulatory mechanism to control how PRMT1 performs its job inside the cell. In the second aim, the project will determine the mechanistic role of a portion of PRMT1 called the tail. Of the 11 different kinds of PRMTs, the tails on each of the enzymes are very different; suggesting that the tail may be involved in specifying which proteins should be targeted by each PRMT. The results will provide a framework for studying the other PRMT enzymes. These studies will be a much needed counterpart to the cell biological approaches that predominate in the field of PRMTs. Broader Impacts The inclusion of undergraduates in the research endeavor will be a primary focus of the PI. In addition to undergraduates mentored personally by the PI, portions of the research will be conducted by students in the senior-level undergraduate Biochemistry laboratory course. Web-based reporting will allow students to track the progress of the research providing context for the experiment. These efforts will help to transform the outdated laboratory course into a more interactive and novel experience for the students. The PI will continue to participate in an Undergraduate Research Program to reach students at institutions that do not have internal research opportunities. As a form of outreach to K-12 education, the PI will continue to participate in the development and implementation of the Department's high school summer research program, from which students will be selected and incorporated into the multi-disciplinary research team over the duration of the project. In summary, the PI will integrate the training of graduate, undergraduate, and high school students with high level research efforts that will answer fundamental questions about the biochemistry of PRMT1.