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'''Research Summary'''
'''Research Summary'''


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


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.
'''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.


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.
'''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.


[[Pan Lab |Main]] | [[Pan:What we do|What we do]] | [[Pan:Who we are|Who we are]] | [[Pan:Publications|Publications]] | [[Pan:Protocols|Protocols]] | [[Pan:Contact us|Contact us]]
<font color=#000000 size=2> [[Pan Lab |Main]] | [[Pan:What we do|What we do]] | [[Pan:Who we are|Who we are]] | [[Pan:Research positions|Research positions]] | [[Pan:Press|Press]] |  [[Pan:Publications|Publications]] | [[Pan:Protocols|Protocols]] | [[Pan:Links|Links]] | [[Pan:Contact us|Contact us]]

Revision as of 07:44, 6 March 2017

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.


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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