Prof. Donna J. Koslowsky's lab

This laboratory investigates the regulation of mitochondrial gene expression in the protozoan parasite, Trypanosoma brucei. The protein coding regions of the mitochondrial mRNAs undergo extensive, post-transcriptional editing before they can be translated. This process involves both the insertion and deletion of U residues and occurs at hundreds of specific sites in 12 different mRNAs. The precise sequence alterations are guided by a hundreds of short RNA molecules (the guide RNAs), which are complementary to the mature message. Guide RNAs are key components of the editing reaction as they supply the information for the nucleotide alterations and are able to direct the cleavage and ligation events. Therefore, understanding the nature and relative importance of the elements that confer affinity, as well as specificity on this interaction is critical to our understanding of the editing process. Research in this lab involves defining the structure/function relationships of the RNAs and proteins involved in the editing process with an emphasis on the core structure formed by the gRNA/mRNA pair. Because no common sequence elements have been found, it is assumed that Editosome assembly requires the formation of a common core architecture that can be recognized by the editing complex. In kRNA editing however, the structure itself must be very dynamic as each round of editing changes the sequence of the RNA involved in the reaction.

Undergraduate students supported by the UBM program in this lab will participate in deriving both a quantitative and qualitative description of how the different structural domains of the guide RNA contribute to the specificity and affinity of the RNA editing reaction. Using ITC (isothermal calorimetry) and Surface Plasmon Resonance combined with Structure modeling techniques and site-specific mutagenesis, the students should be able to quantify the importance of the different domains in the editing process.

Lab Home Page: http://www.msu.edu/unit/mic/facpages/koslowsk.html