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


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


tRNA is essential for protein synthesis and life. Biological genomes contain up to several hundred tRNA genes. Translational regulation is related to the dynamic properties of each tRNA that constantly change to facilitate stress response and cellular adaptation to new environments and to control gene expression in differentiated organisms. We have developed tRNA microarrays that measure the abundance and the fraction of aminoacylation of each tRNA. Using these microarray technologies, we are exploring the effect of varying tRNA concentration and aminoacylation fraction on translation in bacteria and in cancer cells.  
'''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.


Over 100 chemical types of post-transcriptional modifications have been identified in thousands of sites in RNAs 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 are working on a general microarray method that will detect and quantify the extent of modifications in any RNA. We are applying this high throughput, microarray method to study the function of RNA modifications at the genomic level during cell growth, adaptation and development. 


The goals of RNA folding are to understand how RNA folds into defined structures and how RNA structures are stabilized. We use a wide array of biophysical, structural and biochemical methods to elucidate the principles RNA folding and stability. Folding during transcription is also studied to mimic RNA folding in the cell.
'''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.


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