Tao Pan, Ph.D.

Biology of Mistranslation , RNA Epigenetics, RNA Folding

Research Summary

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 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.

Lab website: http://openwetware.org/wiki/Pan_Lab

Selected Papers

Zaborske, J.M., J. Narasimhan, L. Jiang, S.A. Wek, K.A. Dittmar, F. Freimoser, Tao Pan* & R.C. Wek* (2009). Genome-wide analysis of tRNA charging and activation of the eIF2 kinase Gcn2p, J. Biol. Chem. 284, 25254-25267.

Pavon-Eternod, M., S. Gomes, R. Geslain, Q. Dai, M.R. Rosner* & Tao Pan* (2009). tRNA Over-expression in Breast Cancer and Functional Consequences, Nucl. Acids Res. 37, 7268-7280.

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* (2009). Innate Immune and Chemically Triggered Oxidative Stress Modifies Translational Fidelity, Nature 462, 522-526.

Pavon-Eternod, M., M. Wei, Tao Pan* & Lawrence Kleiman* (2010). Profiling non-lysyl tRNAs in HIV-1, RNA 16, 267-273.

Geslain, R. & Tao Pan* (2010). Functional analysis of human tRNA isodecoders, J. Mol. Biol. 396, 821-831.

Baird, N.J., H-P. Gong, S.S. Zaheer, K.F. Freed, Tao Pan* & T.R. Sosnick* (2010). Extended structures in RNA folding intermediates are due to non-native interactions rather than electrostatic repulsion, J. Mol. Biol. 397, 1298-1306.

Tuller, T., A. Carmi, K. Vestsigian, S. Navon, Y. Dorfan, J. Zaborske, Tao Pan, O. Dahan, I. Furman & Y. Pilpel (2010). An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation, Cell 141, 344-354.

Staschke, K.A., D. Souvik, J. M. Zaborske, L.R. Palam, J. N. McClintick, Tao Pan, H. J. Edenberg & R.C. Wek (2010). Integration of general amino acid control and TOR regulatory pathways in nitrogen assimilation in yeast, J. Biol. Chem. 285, 16893-16911.

Saikia, M., Y. Fu, M. Pavon-Eternod, C. He & Tao Pan* (2010). Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs, RNA 16, 1317-1327.

Zaborske, J.M., X-C. Wu, R. C. Wek, Tao Pan* (2010). Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiae, BMC Biochemistry 11:e29.

Fu, Y., Q. Dai, W. Zhang, J. Ren, Tao Pan* & C. He* (2010). The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-methoxycarbonylmethyluridine at the anticodon wobble base in tRNA, Angewandte Chemie (Int) 49, 8885-8888.

Reiter, N.J., Osterman, A., Torres-Larios, A., Swinger, K.K., Tao Pan & Mondragon, A. (2010). Crystal structure of a bacterial ribonuclease P holoenzyme in complex with tRNA, Nature 468, 784-791.

Baird, N.J., S.J. Ludtke, H. Khant, W. Chiu, Tao Pan* & T.R. Sosnick* (2010). A discrete structure of an RNA folding intermediate revealed by cryo-electron microscopy, J. Am. Chem. Soc. 132, 16352-16353.

Yi, C-Q. & Tao Pan: Cellular Dynamics of RNA modification, Acc. Chem. Res., e-published, May 28 (2011).

Jones, T.E., R.W. Alexander, Tao Pan* (2011). Misacylation of specific non-methionyl-tRNAs by a bacterial methionyl-tRNA synthetases, Proc. Natl. Acad. Sci. USA 108, 6933-6938.

Dai, Q., C-X. Song, Tao Pan & C. He (2011). Syntheses of Two 5-Hydroxymethyl-20-deoxycytidine Phosphoramidites with TBDMS as the 5-Hydroxymethyl Protecting Group and Their Incorporation into DNA, J. Org. Chem. 76, 4182-4188.

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., e-pub. Oct. 16 (2011).

Parisien, M., C-Q. Yi & Tao Pan*: Rationalization and prediction of selective decoding of pseudouridine-modified nonsense and sense codons, RNA, in press (2012).