Research topics: Functional genomics of RNA, RNA epigenetics, 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. 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 developing genome-wide methods and applying these to study the function of RNA modifications in cell growth, adaptation and development.
Non-coding RNAs perform biological function without being translated into proteins. Some estimates suggest that in human, the number of non-coding RNAs may be comparable to the number of coding RNAs. We are investigating how RNA folds during transcription to understand RNA folding in the cell.
Pavon-Eternod, M., S. Gomes, M.R. Rosner* & Tao Pan*: Overexpression of Initiator Methionine tRNA Leads to Global Reprogramming of tRNA Expression and Increased Proliferation in Human Epithelial Cells, RNA, in press (2013).
Li, M-Q., E. Kao, X. Gao, H. Sandig, K. Limmer, M. Pavon Eternod, T. Jones, S. Landry, Tao Pan, M.D. Weitzman & M. David: Codon usage-based Inhibition of HIV Protein Synthesis by Human Schlafen 11, Nature 491, 125-8 (2012).
Zhou, D-H, J-Y. Lee, C. Frankenberger, R. Geslain*, M. Rosner*, Tao Pan*: Anti-tumor effects of an engineered "killer" transfer RNA, Biochem. Biophys. Res. Comm. 427, 148-153 (2012).
Wiltrout, E., J.M. Goodenbour, M. Frechin & Tao Pan*: Misacylation of tRNA with Methionine in Saccharomyces cerevisiae, Nucl. Acids Res. 40, 10494-10506 (2012).
Starck, S.R., V. Jiang, M. Pavon-Eternod, S. Prasad, B. McCarthy, Tao Pan, N. Shastri: Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I, Science 336, 1719-1723 (2012).
Novoa, E.M., M. Pavon Eternod, Tao Pan & L. Ribas de Pouplana: Two anticodon modifications shaped tRNA gene populations and genome structure in bacteria and eukaryotes, Cell 149, 202-13 (2012).
Perdrizet, G.A., I. Artsimovitch, R. Furman, T. R. Sosnick*, Tao Pan*: Transcriptional pausing coordinates folding of the aptamer domain and the expression platform of a riboswitch, Proc. Natl. Acad. Sci. USA 109, 3323-3328 (2012).
Parisien, M., C-Q. Yi & Tao Pan*: Rationalization and prediction of selective decoding of pseudouridine-modified nonsense and sense codons, RNA 18, 355-367 (2012).
Jia, G-F.,Y. Fu, X. Zhao, Q. Dai, G-Q. Zheng, Y. Yang, C-Q. Yi, T. Lindahl, Tao Pan, Y-G. Yang & C. He: N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO, Nature Chem. Biol. 7, 885-887 (2011).
Jones, T.E., R.W. Alexander, Tao Pan*: Misacylation of specific non-methionyl-tRNAs by a bacterial methionyl-tRNA synthetases, Proc. Natl. Acad. Sci. USA 108, 6933-6938 (2011).
Fu, Y., Q. Dai, W. Zhang, J. Ren, Tao Pan* & C. He*: The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-methoxycarbonylmethyluridine at the anticodon wobble base in tRNA, Angewandte Chemie (Int) 49, 8885-8888 (2010).
Saikia, M., Y. Fu, M. Pavon-Eternod, C. He & Tao Pan*: Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs, RNA 16, 1317-1327 (2010).
Tuller, T., A. Carmi, K. Vestsigian, S. Navon, Y. Dorfan, J. Zaborske, Tao Pan, O. Dahan, I. Furman & Y. Pilpel: An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation, Cell 141, 344-354 (2010).
Geslain, R. & Tao Pan*: Functional analysis of human tRNA isodecoders, J. Mol. Biol. 396, 821-831 (2010).
Netzer, N., J.M. Goodenbour, A. David, K.A. Dittmar, R.B. Jones, J.R. Schneider, D. Boone, E.M. Eves, M.R. Rosner, J.S. Gibbs, A. Embry, B. Dolan, S. Das, H. Hickman, P. Berglund, J.R. Bennink, J.W. Yewdell*, Tao Pan*: Innate Immune and Chemically Triggered Oxidative Stress Modifies Translational Fidelity, Nature 462, 522-526 (2009).
Pavon-Eternod, M., S. Gomes, M.R. Rosner* & Tao Pan*: Overexpression of Initiator Methionine tRNA Leads to Global Reprogramming of tRNA Expression and Increased Proliferation in Human Epithelial Cells, RNA, in press (2013).
Li, M-Q., E. Kao, X. Gao, H. Sandig, K. Limmer, M. Pavon Eternod, T. Jones, S. Landry, Tao Pan, M.D. Weitzman & M. David: Codon usage-based Inhibition of HIV Protein Synthesis by Human Schlafen 11, Nature 491, 125-8 (2012).
Zhou, D-H, J-Y. Lee, C. Frankenberger, R. Geslain*, M. Rosner*, Tao Pan*: Anti-tumor effects of an engineered "killer" transfer RNA, Biochem. Biophys. Res. Comm. 427, 148-153 (2012).
Wiltrout, E., J.M. Goodenbour, M. Frechin & Tao Pan*: Misacylation of tRNA with Methionine in Saccharomyces cerevisiae, Nucl. Acids Res. 40, 10494-10506 (2012).
Starck, S.R., V. Jiang, M. Pavon-Eternod, S. Prasad, B. McCarthy, Tao Pan, N. Shastri: Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I, Science 336, 1719-1723 (2012).
