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Our research focuses on
elucidating principles of RNA folding and functional genomics of tRNA. |+|
Our research focuses on functional genomics of tRNA.
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|-|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. |+|
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|-|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. |+|
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|-|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. |+|
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Our research focuses on functional genomics of tRNA, RNA epigenetics and RNA folding.
Translational regulation is related to the dynamic properties of tRNA that constantly change to facilitate stress response and adaptation to new environments and to control gene expression. We developed microarray methods that measure tRNA abundance, fraction of aminoacylation and misacylation at the genomic scale. We are exploring roles of tRNA in translational control in mammalian cells.
A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is avoided at all times. We discovered that mammalian cells can deliberately reprogram the genetic code through tRNA misacylation upon innate immune activation and chemically triggered oxidative stress. The reprogramming is regulated by fluctuating levels of reactive oxygen species (ROS) in the cell. We are investigating how regulated mis-translation is used as a mechanism for stress response.
Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites from bacteria to humans. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, addition of ring structures and carbohydrate moieties, and so on. RNA modifications are involved in stress response, environmental adaptation, and antibiotic resistance. Some modifications can be removed by cellular enzymes, leading to dynamic regulation of their function. We are investigating the function of RNA modifications in cell growth, adaptation and development.
We are also investigating how RNA folds during transcription to understand RNA folding and structural rearrangement in the cell.
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