Pan:What we do
Our research focuses on elucidating principles of RNA folding and functional genomics of tRNA.
The goals of RNA folding studies are to understand how RNA folds into defined structures and to rationally design RNA structures of high stability. We apply an array of biophysical and biochemical methods including single-molecule fluorescence spectroscopy to evaluate RNA folding and stability. Folding during transcription is also studied to mimic RNA folding in vivo.
Transfer RNA is essential for protein synthesis and life. Biological genomes contain 23 - 500 tRNA genes encoding 23 - 57 unique tRNA species. Translational regulation of any protein is related to three properties of each tRNA: concentration, fraction of aminoacylation, and post-transcriptional modification. For example, highly abundant ribosomal proteins have strong codon biases that correlate with tRNA isoacceptors of highest concentration. Upon environmental change, the fraction of aminoacylation can be selectively altered for each tRNA isoacceptor, allowing more efficient translation of regulatory proteins whose mRNAs contain unique sets of codons.
We have developed a microarray specifically tailored for tRNA. The microarray allows the measurement of relative concentration of each tRNA between two samples and the absolute fraction of aminoacylation of each tRNA in the same sample. Using this microarray, we are exploring the effect of varying tRNA concentration and aminoacylation fraction on translation in bacteria and in cancer cells. We are also developing microarrays for quantitative measurements of all post-transcriptional modifications.