Deborah A. Steege
Professor Emeritus of Biochemistry

Research in the laboratory is focused on controls of gene expression at steps after initiation of transcription, which are increasingly recognized as important means of regulation. We are using biochemical and genetic techniques to define the RNA-RNA and RNA-protein interactions which mediate such regulation. At present, we are particularly interested in a set of genes which are encoded by polycistronic mRNAs but expressed at markedly different levels from the same mRNA molecule. One area explores stratagies of translational control. Experiments are in progress to demonstrate the mechanism of translational coupling between two of the genes and to determine more generally how coupling is used either to coordinate expression of two adjacent genes or to downregulate expression from one to the next. In a new line of inquiry we are exploring the principles that govern the relative levels at which in-frame overlapping genes are translated from the polycistronic mRNAs. We are also initiating analysis of an extraordinarily efficient tranlational start site which appears to be enhancer-driven and hence has the potential to reveal previously unrecognized interactions between mRNA and the ribosome. The second area of interest concerns polyadenylation and processing of the mRNAs. The ;principal processing enzyme is RNase E,the first endoribonuclease shown to have a global role in mRNA stability and one that resides in a large macromolecular complex called the degradosome. Through study of strains deficient in poly(A) polymerase and/or RNase E, the pathways the mRNAs follow from their initial synthesis, processing, to their ultimate decay have emerged. We also have obtained evidence that the normal processing pathway has several biological functions. By setting the steady state levels of the mRNAs, it sets the appropriate ratios of two essential DNA replication proteins made from the overlapping genes. Later, it provides longer-lived mRNA templates for proteins needed in large amounts, and delays inactivation of the coding region for the most abundant protein. Students and postdoctoral fellows have always been the key contributors to all aspects or our research program.

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