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Office: (859) 257-5478
Fax: (859) 257-8994
Lab: (859) 257-4879
Email: mlpete01@uky.edu
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Martha Peterson, Ph.D.
Professor
Doctoral Studies: University of Wisconsin-Madison.
Postdoctoral: Fox Chase Cancer Center.
Research Statement:
Gene expression regulation is a complex process that occurs at multiple steps of the gene expression pathway. While transcription initiation begins the process of gene expression, the post-transcriptional steps of RNA splicing, cleavage-polyadenylation, transport and stability all contribute to the type and final levels of protein that will be produced. In addition, these steps are coupled to each other and to the process of transcription elongation and termination; how this coupling occurs and is regulated is not yet clear. My lab has been studying several different model systems that allow us to address questions of how specific post-transcriptional events are regulated and coupled to each other.
Alternative RNA processing creates a vast diversity of protein products from the surprisingly small number of genes in the human genome; as many as 80% of all genes may be alternatively processed. My lab has been studying the mRNAs encoding the secreted and membrane-bound forms of IgM as a model system to understand developmentally regulated RNA processing. A common precursor RNA is differentially processed at its 3' end to produce these two mRNAs and the pattern of RNA processing varies during B cell development. The regulation of these mRNAs involves a competition between two mutually exclusive RNA processing reactions: cleavage-polyadenylation and RNA splicing. In addition, we have discovered an RNA polymerase II pause site downstream from the secretory-specific poly(A) site that contributes to the balance between the alternative RNA processing reactions. We continue to study the regulation of and connections between the RNA processing and transcription elongation and termination reactions.
In collaboration with the Spear lab, we have been studying the repression of AFP expression that occurs in the mouse liver after birth. By mapping the gene responsible for a natural mouse mutation that leads to incomplete AFP repression, we have identified Zhx2 to be a factor involved in this process. While the promoter of AFP is required for Zhx2-mediated postnatal repression, we have shown that transcription rates do not differ between mice with or without Zhx2. Rather, RNA splicing is inhibited, contributing to the reduction in mRNA. This appears to be a novel regulatory mechanism that couples transcription to a post-transcriptional step of gene expression. We are using tissue culture cell lines as well as transgenic mice to learn more about B cell alternative RNA processing and gene repression during liver development.
Selected Recent Publications:
Burnside, R., A. Ribble and M.L. Peterson (2009) The spatial relationship between RNA polymerase II pause sites and poly(A) signals in the mouse IgM gene. Under revision.
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