- Professor, Dept. of Biochemistry & Molecular Biology, University of Chicago
Department of Biochemistry & Molecular Biology
The University of Chicago
929 E. 57th St., GCIS W134
Chicago, IL 60637
Phone: 773 702 4179
Fax: 773 702 4179
tRNA is essential for protein synthesis and life. Genomes contain hundreds of tRNA genes. Translational regulation is related to the dynamic properties of tRNA that constantly change to facilitate stress response and cellular adaptation to new environments and to control gene expression in differentiated organisms. We developed microarray methods that measure tRNA abundance, its fraction of aminoacylation and misacylation at the genomic scale. We are exploring roles of tRNA in translational control in yeast and in mammalian cells including cancer. Over 100 types of post-transcriptional modifications have been identified in thousands of RNA sites from bacteria to man. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, elaborate addition of ring structures and carbohydrate moieties, and so on. RNA modification enzymes represent 1-2% of all genes in bacteria. Hundreds of guide RNAs and dozens of proteins are used to direct modifications in eukaryotic rRNAs. RNA modifications are involved in stress response, environmental adaptation, antibiotic resistance and human neurology. We developed genomic methods that detect and quantify changes in modification fraction. We are applying these high throughput methods to study the function of RNA modifications at the genomic level during cell growth, adaptation and development. Non-coding RNAs perform biological function without being translated into proteins. Some estimates suggest that in human, the number of non-coding RNAs may be comparable to the number of coding RNAs. We are working on methods for folding studies of non-coding RNAs, and for structural determination using cryo-Electron Microscopy. Folding during transcription is also studied to understand non-coding RNA folding in the cell..