Pan:What we do

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Research Summary

Our research focuses on functional genomics and the biology of tRNA and epitranscriptomics (aka RNA epigenetics).

tRNA biology: 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 high throughput sequencing methods (DM-tRNA-seq) that measure tRNA abundance, charging fraction and quantify modification fractions. We are investigating the roles of tRNA in translational control and extra-translational functions in mammalian cells. A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. In contrast to common beliefs, we discovered that cells in all three domains of life (mammals, bacteria, hyperthermophilic archaea) can deliberately reprogram the genetic code through tRNA misacylation under selective conditions. We are investigating how regulated mis-translation (aka adaptive mistranslation) is used as a mechanism for stress response.

Microbiome: We are also applying our tRNA-seq technology as another approach for microbiome characterization. Standard microbiome characterizations include 16S-seq or shotgun metagenomics. Although powerful, these DNA-based methods do not directly report the microbiome activity such as dynamic gene expression where RNA studies are better suited. Our microbiome tRNA-seq results show extensive variations of tRNA abundance and modification patterns in microbiomes from different sources, indicating that tRNA-seq can provide new insights in microbiome dynamics. We are further developing this approach to explore the potentials of tRNA-seq to study microbiome activities.

Epitranscriptomics: Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites in all cells. 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. mRNA modifications are involved in cell differentiation, proliferation, and many other cellular functions. tRNA and rRNA modifications are involved in stress response, environmental adaptation, and antibiotic resistance. Certain mRNA and tRNA modifications can be removed by cellular enzymes, leading to dynamic regulation of their functions. We are investigating the function of RNA modifications in cell growth, adaptation and development. For N6-methyladenosine (m6A) modifications in mRNAs, we discovered that m6A modification can alter the local mRNA secondary structure to regulate binding of mRNA binding proteins transcriptome-wide (m6A switch). The m6A switch mechanism significantly affects mRNA abundance and alternative splicing. We are also developing sequencing methods that can identify mRNA modifications at single base resolution, quantify their modification fractions, and require only minute amount of input material.

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