RNA Groups
at the
University of Michigan

David R. Engelke    

Professor of Biological Chemistry
Director, Program in Biomedical Sciences


My laboratory investigates several aspects of eukaryotic gene expression, using yeast and human model systems. A combination of biochemistry, molecular genetics, and high resolution microscopy is used to study the forces that both activate and silence nuclear transcription units. We recently found that tRNA genes antagonize transcription of other nearby promoters, and that this phenomenon is related to the three dimensional organization of the activated transcription units. This phenomenon is under study as a potentially widespread negative regulatory mechanism. In addition to transcription mechanisms, the lab studies structures and functions of RNA enzymes, especially the ubiquitous endoribonuclease RNase P. The highly ordered tertiary structures of the RNA enzymes recognize and cleave pre-tRNA and other substrates through shape recognition, and the nuclear form of RNase P has developed an elaborate subunit structure to allow discrimination of its role in the complex nuclear RNA processing pathways. We are studying how this complex holoenzyme structure recognizes both substrates and elements of the nuclear architecture.

In related projects, we are exploring the ability of nucleic acid chains to recognize a variety of molecular targets, and to apply this knowledge to practical problems. It has become possible to select RNA (or modified RNA) molecules that bind tightly to nearly any molecular surface, starting from a "library" of more than a quadrillion sequences. This allows the production of affinity tags, diagnostics, and potentially potent inhibitors to a wide variety of targets that are not necessarily amenable to antibody production.



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