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Yang, Xiang-Lei
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Yang, Xiang-Lei

Faculty Member
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Positions

  • 2017 - Professor, Molecular Medicine , Scripps Research
  • 2000 - Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2014 - 2017 Professor, Chemical Physiology , Scripps Research
  • 2013 - 2014 Associate Professor, Chemical Physiology , Scripps Research
  • 2013 - 2014 Associate Professor (Joint Appointment), Cell and Molecular Biology (CMB) , Scripps Research
  • 2000 - 2012 Associate Professor (Joint Appointment), Molecular Biology , Scripps Research
Dr. Xiang-Lei Yang is elucidating the functional diversity of mammalian aminoacyl-tRNA synthetases in signal transduction pathways involving angiogenesis, neurogenesis, inflammation and apoptosis, and how the different functions of aminoacyl-tRNA synthetases are activated and regulated.

Research Areas research areas

  • Alzheimer (UMLS)
  • Blindness (UMLS)

Contact

  • xlyang@scripps.edu

Websites

  • Xiang-Lei Yang, Ph.D.
  • Laboratory Website
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Publications

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    • Zhao, J., Bai, H. M., Li, X. Y., Yan, J., Zou, G. Y., Wang, L. L., Li, X. R., Liu, Z., Xiang, R., Yang, X. L., Shi, Y. Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer Signal Transduction and Targeted Therapy  2021 6  DOI:10.1038/s41392-021-00714-0  PMID:34400610  PMCID:PMC8368063
    • Chen, B. Y., Luo, S. T., Zhang, S. X., Ju, Y. C., Gu, Q., Xu, J., Yang, X. L., Zhou, H. H. Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase Nature Communications  2021 12  DOI:10.1038/s41467-021-21902-0  PMID:33712620  PMCID:PMC7955072
    • Ju, Y. C., Han, L., Chen, B. Y., Luo, Z. T., Gu, Q., Xu, J., Yang, X. L., Schimmel, P., Zhou, H. H. X-shaped structure of bacterial heterotetrameric tRNA synthetase suggests cryptic prokaryote functions and a rationale for synthetase classifications Nucleic Acids Research  2021 49:10106-10119  DOI:10.1093/nar/gkab707  PMID:34390350  PMCID:PMC8464048
    • Zhang, H., Yang, X. L., Sun, L. T. The uniqueness of AlaRS and its human disease connections RNA Biology  2020 1-11  DOI:10.1080/15476286.2020.1861803  PMID:33317386
    • Shi, Y., Liu, Z., Zhang, Q., Vallee, I., Mo, Z. Y., Kishi, S., Yang, X. L. Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis PLoS Biology  2020 18  DOI:10.1371/journal.pbio.3000991  PMID:33351793  PMCID:PMC7755189
    • Wang, J., Vallee, I., Dutta, A., Wang, Y., Mo, Z., Liu, Z., Cui, H., Su, A. I., Yang, X. L. Multi-Omics Database Analysis of Aminoacyl-tRNA Synthetases in Cancer Genes  2020 11  DOI:10.3390/genes11111384  PMID:33266490  PMCID:PMC7700366
    • Chen, M. R., Kuhle, B., Diedrich, J., Liu, Z., Moresco, J. J., Yates III, J. R., Pan, T., Yang, X. L. Cross-editing by a tRNA synthetase allows vertebrates to abundantly express mischargeable tRNA without causing mistranslation Nucleic Acids Research  2020 48:6445-6457  DOI:10.1093/nar/gkaa469  PMID:32484512  PMCID:PMC7337962
    • Adams, R. A., Fernandes-Cerqueira, C., Notarnicola, A., Mertsching, E., Xu, Z. W., Lo, W. S., Ogilvie, K., Chiang, K. P., Ampudia, J., Rosengren, S., Cubitt, A., King, D. J., et al. Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses Cellular & Molecular Immunology  2019 18:1463-1475  DOI:10.1038/s41423-019-0331-0  PMID:31797905  PMCID:PMC8166958
    • Morelli, K. H., Griffin, L. B., Pyne, N. K., Wallace, L. M., Fowler, A. M., Oprescu, S. N., Takase, R., Wei, N., Meyer-Schuman, R., Mellacheruvu, D., Kitzman, J. O., Kocen, S. G., et al. Allele-specific RNA interference prevents neuropathy in Charcot-Marie-Tooth disease type 2D mouse models Journal of Clinical Investigation  2019 129:5568-5583  DOI:10.1172/jci130600  PMID:31557132  PMCID:PMC6877339
    • Bervoets, S., Wei, N., Erfurth, M. L., Yusein-Myashkova, S., Ermanoska, B., Mateiu, L., Asselbergh, B., Blocquel, D., Kakad, P., Penserga, T., Thomas, F. P., Guergueltcheva, V., et al. Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy Nature Communications  2019 10  DOI:10.1038/s41467-019-12909-9  PMID:31695036  PMCID:PMC6834567
    • Blocquel, D., Sun, L., Matuszekc, Z., Li, S., Weber, T., Kuhle, B., Kooi, G., Wei, N., Baets, J., Pan, T., Schimmel, P., Yang, X. L. CMT disease severity correlates with mutation-induced open conformation of histidyl-tRNA synthetase, not aminoacylation loss, in patient cells Proceedings of the National Academy of Sciences of the United States of America  2019 116:19440-19448  DOI:10.1073/pnas.1908288116  PMID:31501329
    • Wei, N., Zhang, Q., Yang, X. L. Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases Journal of Biological Chemistry  2019 294:5321-5339  DOI:10.1074/jbc.REV118.002955  PMID:30643024  PMCID:PMC6462521
    • Kanaji, T., Vo, M. N., Kanaji, S., Zarpellon, A., Shapiro, R., Morodomi, Y., Yuzuriha, A., Eto, K., Belani, R., Do, M. H., Yang, X. L., Ruggeri, Z. M., et al. Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis accelerating recovery from thrombocytopenia Proceedings of the National Academy of Sciences of the United States of America  2018 115:EB228-EB235  DOI:10.1073/pnas.1807000115  PMID:30104364  PMCID:PMC6126720
    • Chong, Y. E., Guo, M., Yang, X. L., Kuhle, B., Naganuma, M., Sekine, S., Yokoyama, S., Schimmel, P. Distinct ways of G:U recognition by conserved tRNA binding motifs Proceedings of the National Academy of Sciences of the United States of America  2018 115:7527-7532  DOI:10.1073/pnas.1807109115  PMID:29967150  PMCID:PMC6055181
    • Xu, Z., Lo, W. S., Beck, D. B., Schuch, L. A., Olahova, M., Kopajtich, R., Chong, Y. E., Alston, C. L., Seidl, E., Zhai, L., Lau, C. F., Timchak, D., et al. Bi-allelic mutations in phe-tRNA synthetase associated with a multi-system pulmonary disease Support non-translational function American Journal of Human Genetics  2018 103:100-114  DOI:10.1016/j.ajhg.2018.06.006  PMID:29979980  PMCID:PMC6035289
    • Limsakul, P., Peng, Q., Wu, Y., Allen, M. E., Liang, J., Remacle, A. G., Lopez, T., Ge, X., Kay, B. K., Zhao, H. M., Strongin, A. Y., Yang, X. L., et al. Directed evolution to engineer monobody for FRET biosensor assembly and imaging at live-cell surface Cell Chemical Biology  2018 25:370-+  DOI:10.1016/j.chembiol.2018.01.002  PMID:29396288  PMCID:PMC5910193
    • Mo, Z., Zhao, X., Liu, H., Hu, Q., Chen, X. Q., Pham, J., Wei, N., Liu, Z., Zhou, J., Burgess, R. W., Pfaff, S. L., Caskey, C. T., et al. Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy Nature Communications  2018 9  DOI:10.1038/s41467-018-03461-z  PMID:29520015  PMCID:PMC5843656
    • Xu, X., Zhou, H., Zhou, Q., Hong, F., Vo, M. N., Niu, W., Wang, Z., Xiong, X., Nakamura, K., Wakasugi, K., Schimmel, P., Yang, X. L. An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function Rna Biology  2018 15:649-658  DOI:10.1080/15476286.2017.1377868  PMID:28910573  PMCID:PMC6103731
    • Sleigh, J. N., Gomez-Martin, A., Wei, N., Bai, G., Yang, X. L., Schiavo, G. Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular homeostasis Scientific Reports  2017 7  DOI:10.1038/s41598-017-10005-w
    • Blocquel, D., Li, S., Wei, N., Daub, H., Sajish, M., Erfurth, M. L., Kooi, G., Zhou, J., Bai, G., Schimmel, P., Jordanova, A., Yang, X. L. Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy Nucleic Acids Research  2017 45:8091-8104  DOI:10.1093/nar/gkx455  PMID:28531329
    • Sleigh, J. N., Dawes, J. M., West, S. J., Wei, N., Spauldingd, E. L., Gomez-Martin, A., Zhang, Q., Burgess, R. W., Cader, M. Z., Talbot, K., Yang, X. L., Bennett, D. L., et al. Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations Proceedings of the National Academy of Sciences of the United States of America  2017 114:E3324-E3333  DOI:10.1073/pnas.1614557114  PMID:28351971  PMCID:PMC5402433
    • Shi, Y., Wei, N., Yang, X. L. Studying nuclear functions of aminoacyl tRNA synthetases Methods  2017 113:105-110  DOI:10.1016/j.ymeth.2016.09.011  PMID:27664293  PMCID:PMC5300860
    • Sun, L., Song, Y., Blocquel, D., Yang, X. L., Schimmel, P. Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS Proceedings of the National Academy of Sciences of the United States of America  2016 113:14300-14305  DOI:10.1073/pnas.1617316113  PMID:27911835  PMCID:PMC5167178
    • Sun, L., Gomes, A. C., He, W., Zhou, H., Wang, X., Pan, D. W., Schimmel, P., Pan, T., Yang, X. L. Evolutionary gain of alanine mischarging to noncognate tRNAs with a G4:U69 base pair Journal of the American Chemical Society  2016 138:12948-12955  DOI:10.1021/jacs.6b07121  PMID:27622773
    • Mo, Z., Zhang, Q., Liu, Z., Lauer, J., Shi, Y., Sun, L., Griffin, P. R. Neddylation requires glycyl-tRNA synthetase to protect activated E2 Nature Structural & Molecular Biology  2016 23:730-737  DOI:10.1038/nsmb.3250  PMID:27348078  PMCID:PMC4972647
    • Wei, Z., Xu, Z., Liu, X., Lo, W. S., Ye, F., Lau, C. F., Wang, F., Zhou, J. J., Nangle, L. A., Yang, X. L., Zhang, M., Schimmel, P. Alternative splicing creates two new architectures for human tyrosyl-tRNA synthetase Nucleic Acids Research  2016 44:1247-1255  DOI:10.1093/nar/gkw002  PMID:26773056  PMCID:PMC4756856
    • He, W., Bai, G., Zhou, H., Wei, N., White, N. M., Lauer, J., Liu, H., Shi, Y., Dumitru, C. D., Lettieri, K., Shubayev, V., Jordanova, A., et al. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase Nature  2015 526:710-714  DOI:10.1038/nature15510  PMID:26503042  PMCID:PMC4754353
    • Niehues, S., Bussmann, J., Steffes, G., Erdmann, I., Kohrer, C., Sun, L., Wagner, M., Schafer, K., Wang, G., Koerdt, S. N., Stum, M., RajBhandary, U. L., et al. Impaired protein translation in Drosophila models for Charcot-Marie-Tooth neuropathy caused by mutant tRNA synthetases Nature Communications  2015 6:7520  DOI:10.1038/ncomms8520  PMID:26138142  PMCID:PMC4506996
    • Yang, X. L. tRNA-derived G-quadruplex protects motor neurons Proceedings of the National Academy of Sciences of the United States of America  2014 111:18108-18109  DOI:10.1073/pnas.1420838111  PMID:25512555  PMCID:PMC4280617
    • Wei, N., Shi, Y., Truong, L. N., Fisch, K. M., Xu, T., Gardiner, E., Fu, G., Hsu, Y. S. O., Kishi, S., Su, A. I., Wu, X., Yang, X. L. Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage Molecular Cell  2014 56:323-332  DOI:10.1016/j.molcel.2014.09.006  PMID:25284223  PMCID:PMC4224670
    • Ishimura, R., Nagy, G., Dotu, I., Zhou, H., Yang, X. L., Schimmel, P., Senju, S., Nishimura, Y., Chuang, J. H., Ackerman, S. L. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration Science  2014 345:455-459  DOI:10.1126/science.1249749  PMID:25061210  PMCID:PMC4281038
    • Lo, W. S., Gardiner, E., Xu, Z., Lau, C. F., Wang, F., Zhou, J. J., Mendlein, J. D., Nangle, L. A., Chiang, K. P., Yang, X. L., Au, K. F., Wong, W. H., et al. Human tRNA synthetase catalytic nulls with diverse functions Science  2014 345:328-332  DOI:10.1126/science.1252943  PMID:25035493  PMCID:PMC4188629
    • Zhou, J. J., Wang, F., Xu, Z., Lo, W. S., Lau, C. F., Chiang, K. P., Nangle, L. A., Ashlock, M. A., Mendlein, J. D., Yang, X. L., Zhang, M., Schimmel, P. Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis Journal of Biological Chemistry  2014 289:19269-19275  DOI:10.1074/jbc.C114.571026  PMID:24898250  PMCID:PMC4094037
    • Naganuma, M., Sekine, S., Chong, Y. E., Guo, M., Yang, X. L., Gamper, H., Hou, Y. M., Schimmel, P., Yokoyama, S. The selective tRNA aminoacylation mechanism based on a single G.U pair Nature  2014 510:507-511  DOI:10.1038/nature13440  PMID:24919148  PMCID:PMC4323281
    • Shi, Y., Xu, X., Zhang, Q., Fu, G., Mo, Z., Wang, G. S., Kishi, S., Yang, X. L. tRNA synthetase counteracts c-Myc to develop functional vasculature Elife  2014 3:e02349  DOI:10.7554/eLife.02349  PMID:24940000  PMCID:PMC4057782
    • Guo, M., Yang, X. L. Architecture and metamorphosis Topics in Current Chemistry  2014 344:89-118  DOI:10.1007/128_2013_424  PMID:23536245  PMCID:PMC3864538
    • Xu, X., Shi, Y., Yang, X. L. Crystal structure of human seryl-tRNA synthetase and Ser-SA complex reveals a molecular lever specific to higher eukaryotes Structure  2013 21:2078-2086  DOI:10.1016/j.str.2013.08.021  PMID:24095058  PMCID:PMC3825832
    • Gonzalez, M., McLaughlin, H., Houlden, H., Guo, M., Yo-Tsen, L., Hadjivassilious, M., Speziani, F., Yang, X. L., Antonellis, A., Reilly, M. M., Zuchner, S., Inherited Neuropathy Consortium (INC) Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2 Journal of Neurology Neurosurgery and Psychiatry  2013 84:1247-1249  DOI:10.1136/jnnp-2013-305049  PMID:23729695  PMCID:PMC3796032
    • Wang, F., Xu, Z., Zhou, J., Lo, W. S., Lau, C. F., Nangle, L. A., Yang, X. L., Zhang, M., Schimmel, P. Regulated capture by exosomes of mRNAs for cytoplasmic tRNA synthetases Journal of Biological Chemistry  2013 288:29223-29228  DOI:10.1074/jbc.C113.490599  PMID:24003230  PMCID:PMC3795223
    • Yang, X. L. Structural disorder in expanding the functionome of aminoacyl-tRNA synthetases Chemistry & Biology  2013 20:1093-1099  DOI:10.1016/j.chembiol.2013.07.013  PMID:24054183  PMCID:PMC3782743
    • Zhou, H. H., Sun, L. T., Yang, X. L., Schimmel, P. ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase Nature  2013 494:121-124  DOI:10.1038/nature11774  PMID:23263184  PMCID:PMC3569068
    • Ofir-Birin, Y., Fang, P. F., Bennett, S. P., Zhang, H. M., Wang, J., Rachmin, I., Shapiro, R., Song, J., Dagan, A., Pozo, J., Kim, S., Marshall, A. G., et al. Structural switch of lysyl-tRNA synthetase between translation and transcription Molecular Cell  2013 49:30-42  DOI:10.1016/j.molcel.2012.10.010  PMID:23159739  PMCID:PMC3766370
    • Xu, Z. W., Wei, Z. Y., Zhou, J. J., Ye, F., Lo, W. S., Wang, F., Lau, C. F., Wu, J. J., Nangle, L. A., Chiang, K. P., Yang, X. L., Zhang, M. J., et al. Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing Structure  2012 20:1470-1477  DOI:10.1016/j.str.2012.08.001  PMID:22958643  PMCID:PMC3485694
    • Lee, P. S., Zhang, H. M., Marshall, A. G., Yang, X. L., Schimmel, P. Uncovering of a short internal peptide activates a tRNA synthetase procytokine Journal of Biological Chemistry  2012 287:20504-20508  DOI:10.1074/jbc.C112.369439  PMID:22549774  PMCID:PMC3370235
    • Sajish, M., Zhou, Q. S., Kishi, S., Valdez, D. M., Kapoor, M., Guo, M., Lee, S., Kim, S., Yang, X. L., Schimmel, P. Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling Nature Chemical Biology  2012 8:547-554  DOI:10.1038/nchembio.937  PMID:22504299  PMCID:PMC3780985
    • Fu, G. S., Xu, T., Shi, Y., Wei, N., Yang, X. L. tRNA-controlled nuclear import of a human tRNA synthetase Journal of Biological Chemistry  2012 287:9330-9334  DOI:10.1074/jbc.C111.325902  PMID:22291016  PMCID:PMC3308776
    • Park, M. C., Kang, T., Jin, D., Han, J. M., Kim, S. B., Park, Y. J., Cho, K., Park, Y. W., Guo, M., He, W., Yang, X. L., Schimmel, P., et al. Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis Proceedings of the National Academy of Sciences of the United States of America  2012 109:E640-E647  DOI:10.1073/pnas.1200194109  PMID:22345558  PMCID:PMC3306665
    • Xu, X. L., Shi, Y., Zhang, H. M., Swindell, E. C., Marshall, A. G., Guo, M., Kishi, S., Yang, X. L. Unique domain appended to vertebrate tRNA synthetase is essential for vascular development Nature Communications  2012 3:681  DOI:10.1038/ncomms1686  PMID:22353712  PMCID:PMC3293412
    • Motley, W. W., Seburn, K. L., Nawaz, M. H., Miers, K. E., Cheng, J., Antonellis, A., Green, E. D., Talbot, K., Yang, X. L., Fischbeck, K. H., Burgess, R. W. Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels PLoS Genetics  2011 7:e1002399  DOI:10.1371/journal.pgen.1002399  PMID:22144914  PMCID:PMC3228828
    • Yang, X. L., Schimmel, P. Functional expansion of the tRNA world under stress Molecular Cell  2011 43:500-502  DOI:10.1016/j.molcel.2011.08.004  PMID:21855789  PMCID:PMC3163667
    • He, W., Zhang, H. M., Chong, Y. E., Guo, M., Marshall, A. G., Yang, X. L. Dispersed disease-causing neomorphic mutations on a single protein promote the same localized conformational opening Proceedings of the National Academy of Sciences of the United States of America  2011 108:12307-12312  DOI:10.1073/pnas.1104293108  PMID:21737751  PMCID:PMC3145702
    • Fang, P. F., Zhang, H. M., Shapiro, R., Marshall, A. G., Schimmel, P., Yang, X. L., Guo, M. Structural context for mobilization of a human tRNA synthetase from its cytoplasmic complex Proceedings of the National Academy of Sciences of the United States of America  2011 108:8239-8244  DOI:10.1073/pnas.1100224108  PMID:21536907  PMCID:PMC3100937
    • Vo, M. N., Yang, X. L., Schimmel, P. Dissociating quaternary structure regulates cell-signaling functions of a secreted human tRNA synthetase Journal of Biological Chemistry  2011 286:11563-11568  DOI:10.1074/jbc.C110.213876  PMID:21310955  PMCID:PMC3064210
    • Nawaz, M. H., Merriman, E., Yang, X. L., Schimmel, P. p23(H) implicated as cis/trans regulator of AlaXp-directed editing for mammalian cell homeostasis Proceedings of the National Academy of Sciences of the United States of America  2011 108:2723-2728  DOI:10.1073/pnas.1019400108  PMID:21285375  PMCID:PMC3041069
    • Guo, M., Shapiro, R., Morris, G. M., Yang, X. L., Schimmel, P. Packaging HIV virion components through dynamic equilibria of a human tRNA synthetase Journal of Physical Chemistry B  2010 114:16273-16279  DOI:10.1021/jp1082517  PMID:21058683  PMCID:PMC3042951
    • Han, G. W., Yang, X. L., McMullan, D., Chong, Y. E., Krishna, S. S., Rife, C. L., Weekes, D., Brittain, S. M., Abdubek, P., Ambing, E., Astakhova, T., Axelrod, H. L., et al. Structure of a tryptophanyl-tRNA synthetase containing an iron-sulfur cluster Acta Crystallographica Section F-Structural Biology and Crystallization Communications  2010 66:1326-1334  DOI:10.1107/s1744309110037619  PMID:20944229  PMCID:PMC2954223
    • Guo, M., Yang, X. L., Schimmel, P. New functions of aminoacyl-tRNA synthetases beyond translation Nature Reviews Molecular Cell Biology  2010 11:668-674  DOI:10.1038/nrm2956  PMID:20700144  PMCID:PMC3042954
    • Guo, M., Shapiro, R., Schimmel, P., Yang, X. L. Introduction of a leucine half-zipper engenders multiple high-quality crystals of a recalcitrant tRNA synthetase Acta Crystallographica Section D-Biological Crystallography  2010 66:243-250  DOI:10.1107/s0907444909055462  PMID:20179335  PMCID:PMC2827346
    • Guo, M., Schimmel, P., Yang, X. L. Functional expansion of human tRNA synthetases achieved by structural inventions FEBS Letters  2010 584:434-442  DOI:10.1016/j.febslet.2009.11.064  PMID:19932696  PMCID:PMC2826164
    • Zhou, Q. S., Kapoor, M., Guo, M., Belani, R., Xu, X. L., Kiosses, W. B., Hanan, M., Park, C., Armour, E., Do, M. H., Nangle, L. A., Schimmel, P., et al. Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality Nature Structural & Molecular Biology  2010 17:57-61  DOI:10.1038/nsmb.1706  PMID:20010843  PMCID:PMC3042952
    • Guo, M., Chong, Y. E., Shapiro, R., Beebe, K., Yang, X. L., Schimmel, P. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma Nature  2009 462:808-812  DOI:10.1038/nature08612  PMID:20010690  PMCID:PMC2799227
    • Guo, R. T., Chong, Y. E., Guo, M., Yang, X. L. Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis Journal of Biological Chemistry  2009 284:28968-28976  DOI:10.1074/jbc.M109.030692  PMID:19710017  PMCID:PMC2781443
    • Storkebaum, E., Leitao-Goncalves, R., Godenschwege, T., Nangle, L., Mejia, M., Bosmans, I., Ooms, T., Jacobs, A., Van Dijck, P., Yang, X. L., Schimmel, P., Norga, K., et al. Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy Proceedings of the National Academy of Sciences of the United States of America  2009 106:11782-11787  DOI:10.1073/pnas.0905339106  PMID:19561293  PMCID:PMC2702257
    • Kapoor, M., Otero, F. J., Slike, B. M., Ewalt, K. L., Yang, X. L. Mutational separation of aminoacylation and cytokine activities of human tyrosyl-tRNA synthetase Chemistry & Biology  2009 16:531-539  DOI:10.1016/j.chembiol.2009.03.006  PMID:19477417  PMCID:PMC2706086
    • Guo, M., Chong, Y. E., Beebe, K., Shapiro, R., Yang, X. L., Schimmel, P. The C-Ala domain brings together editing and aminoacylation functions on one tRNA Science  2009 325:744-747  DOI:10.1126/science.1174343  PMID:19661429  PMCID:PMC4559334
    • Chong, Y. E., Yang, X. L., Schimmel, P. Natural homolog of tRNA synthetase editing domain rescues conditional lethality caused by mistranslation Journal of Biological Chemistry  2008 283:30073-30078  DOI:10.1074/jbc.M805943200  PMID:18723508  PMCID:PMC2573062
    • Cheng, G., Zhang, H., Yang, X. L., Tzima, E., Ewalt, K. L., Schimmel, P., Faber, J. E. Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability American Journal of Physiology-Regulatory Integrative and Comparative Physiology  2008 295:R1138-R1146  DOI:10.1152/ajpregu.90519.2008  PMID:18753262
    • Greenberg, Y., King, M., Kiosses, W. B., Ewalt, K., Yang, X., Schimmel, P., Reader, J. S., Tzima, E. The novel fragment of tyrosyl tRNA synthetase, mini-TyrRS, is secreted to induce an angiogenic response in endothelial cells FASEB Journal  2008 22:1597-1605  DOI:10.1096/fj.07-9973com  PMID:18165356
    • Guo, M., Ignatov, M., Musier-Forsyth, K., Schimmel, P., Yang, X. L. Crystal structure of tetrameric form of human lysyl-tRNA synthetase: implications for multisynthetase complex formation Proceedings of the National Academy of Sciences of the United States of America  2008 105:2331-2336  DOI:10.1073/pnas.0712072105  PMID:18272479  PMCID:PMC2268136
    • Kapoor, M., Zhou, Q., Otero, F., Myers, C. A., Bates, A., Belani, R., Liu, J., Luo, J. K., Tzima, E., Zhang, D. E., Yang, X. L., Schimmel, P. Evidence for annexin II-S100A10 complex and plasmin in mobilization of cytokine activity of human TrpRS Journal of Biological Chemistry  2008 283:2070-2077  DOI:10.1074/jbc.M706028200  PMID:17999956
    • Yang, X. L., Kapoor, M., Otero, F. J., Slike, B. M., Tsuruta, H., Frausto, R., Bates, A., Ewalt, K. L., Cheresh, D. A., Schimmel, P. Gain-of-function mutational activation of human tRNA synthetase procytokine Chemistry & Biology  2007 14:1323-1333  DOI:10.1016/j.chembiol.2007.10.016  PMID:18096501  PMCID:PMC2693404
    • Nangle, L. A., Zhang, W., Xie, W., Yang, X. L., Schimmel, P. Charcot-Marie-Tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect Proceedings of the National Academy of Sciences of the United States of America  2007 104:11239-11244  DOI:10.1073/pnas.0705055104  PMID:17595294  PMCID:PMC2040883
    • Yang, X. L., Guo, M., Kapoor, M., Ewalt, K. L., Otero, F. J., Skene, R. J., McRee, D. E., Schimmel, P. Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase Structure  2007 15:793-805  DOI:10.1016/j.str.2007.05.009  PMID:17637340  PMCID:PMC2104486
    • Xie, W., Nangle, L. A., Zhang, W., Schimmel, P., Yang, X. L. Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase Proceedings of the National Academy of Sciences of the United States of America  2007 104:9976-9981  DOI:10.1073/pnas.0703908104  PMID:17545306  PMCID:PMC1891255
    • Xie, W., Schimmel, P., Yang, X. L. Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease Acta Crystallographica Section F-Structural Biology and Crystallization Communications  2006 62:1243-1246  DOI:10.1107/s1744309106046434  PMID:17142907  PMCID:PMC2225372
    • Schimmel, P., Yang, X. L. Perfecting the genetic code with an RNP complex Structure  2006 14:1729-1730  DOI:10.1016/j.str.2006.11.002  PMID:17161363
    • Yang, X. L., Otero, F. J., Ewalt, K. L., Liu, J. M., Swairjo, M. A., Kohrer, C., RajBhandary, U. L., Skene, R. J., McRee, D. E., Schimmel, P. Two conformations of a crystalline human tRNA synthetase–tRNA complex: implications for protein synthesis EMBO Journal  2006 25:2919-2929  DOI:10.1038/sj.emboj.7601154  PMID:16724112  PMCID:PMC1500858
    • Ewalt, K. L., Yang, X. L., Otero, F. J., Liu, J. M., Slike, B., Schimmel, P. Variant of human enzyme sequesters reactive intermediate Biochemistry  2005 44:4216-4221  DOI:10.1021/bi048116l  PMID:15766249
    • Yang, X. L., Schimmel, P., Ewalt, K. L. Relationship of two human tRNA synthetases used in cell signaling Trends in Biochemical Sciences  2004 29:250-256  DOI:10.1016/j.tibs.2004.03.002  PMID:15130561
    • Swairjo, M. A., Otero, F. J., Yang, X. L., Lovato, M. A., Skene, R. J., McRee, D. E., Ribas de Pouplana, L., Schimmel, P. Alanyl-tRNA synthetase crystal structure and design for acceptor-stem recognition Molecular Cell  2004 13:829-841  DOI:10.1016/s1097-2765(04)00126-1  PMID:15053876
    • Schimmel, P., Yang, X. L. Two classes give lessons about CCA Nature Structural & Molecular Biology  2004 11:807-808  DOI:10.1038/nsmb0904-807  PMID:15332079
    • Yang, X. L., Otero, F. J., Skene, R. J., McRee, D. E., Schimmel, P., Ribas de Pouplana, L. Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains Proceedings of the National Academy of Sciences of the United States of America  2003 100:15376-15380  DOI:10.1073/pnas.2136794100  PMID:14671330  PMCID:PMC307575
    • Yang, X. L., Liu, F. M., Skene, R. J., McRee, D. E., Schimmel, P. Crystal structure of an EMAP-II-like cytokine released from a human tRNA synthetase Helvetica Chimica Acta  2003 86:1246-1257  DOI:10.1002/hlca.200390107
    • Liu, J. M., Yang, X. L., Ewalt, K. L., Schimmel, P. Mutational switching of a yeast tRNA synthetase into a mammalian-like synthetase cytokine Biochemistry  2002 41:14232-14237  DOI:10.1021/bi0205395  PMID:12450387
    • Yang, X. L., Skene, R. J., McRee, D. E., Schimmel, P. Crystal structure of a human aminoacyl-tRNA synthetase cytokine Proceedings of the National Academy of Sciences of the United States of America  2002 99:15369-15374  DOI:10.1073/pnas.242611799  PMID:12427973  PMCID:PMC137723
    • Robinson, H., Gao, Y. G., Yang, X. L., Sanishvili, R., Joachimiak, A., Wang, A. H. J. Crystallographic analysis of a novel complex of actinomycin D bound to the DNA decamer CGATCGATCG Biochemistry  2001 40:5587-5592  DOI:10.1021/bi002859z  PMID:11341823
    • Yang, X. L., Robinson, H., Gao, Y. G., Wang, A. H. J. Binding of a macrocyclic bisacridine and ametantrone to CGTACG involves similar unusual intercalation platforms Biochemistry  2000 39:10950-10957  DOI:10.1021/bi001319z  PMID:10998231
    • Yang, X. L., Hubbard, R. B., Lee, M., Tao, Z. F., Sugiyama, H., Wang, A. H. J. Imidazole-imidazole pair as a minor groove recognition motif for T:G mismatched base pairs Nucleic Acids Research  1999 27:4183-4190  DOI:10.1093/nar/27.21.4183  PMID:10518609
    • Yang, X. L., Wang, A. H. J. Structural studies of atom-specific anticancer drugs acting on DNA Pharmacology & Therapeutics  1999 83:181-215  DOI:10.1016/s0163-7258(99)00020-0  PMID:10576292
    • Yang, X. L., Kaenzig, C., Lee, M., Wang, A. H. J. Binding of AR-1-144, a tri-imidazole DNA minor groove binder, to CCGG sequence analyzed by NMR spectroscopy European Journal of Biochemistry  1999 263:646-655  DOI:10.1046/j.1432-1327.1999.00515.x  PMID:10469127
    • Yang, X. L., Sugiyama, H., Ikeda, S., Saito, I., Wang, A. H. J. Structural studies of a stable parallel-stranded DNA duplex incorporating isoguanine:cytosine and isocytosine:guanine basepairs by nuclear magnetic resonance spectroscopy Biophysical Journal  1998 75:1163-1171  DOI:10.1016/S0006-3495(98)74035-4  PMID:9726918  PMCID:PMC1299791
    • Yang, X. L., Wang, A. H. J. Structural analysis of Z-Z DNA junctions with A:A and T:T mismatched base pairs by NMR Biochemistry  1997 36:4258-4267  DOI:10.1021/bi962937b  PMID:9100021
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Research

research overview

  • Our research is focused on elucidating the mechanism of the functional diversity of human aminoacyl-tRNA synthetases and understanding how different functions are activated and regulated.

    Known as an essential component of the translational apparatus, aminoacyl-tRNA synthetase family catalyzes the first step reaction in protein synthesis, that is, to specifically attach each amino acid onto its cognate tRNA. While preserving this essential role, tRNA synthetases develop other roles during evolution. Human tRNA synthetases, in particular, have diverse functions in various pathways involving angiogenesis, inflammation and apoptosis. The functional diversity is further illustrated in the association with various diseases through genetic mutations on tRNA synthetases that do not affect aminoacylation or protein synthesis.

    A cross-disciplinary approach combining biochemical, biophysical, molecular genetics, cell biology and evolutionary analysis is used in our research.
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Teaching

advisees

  • graduate advising relationship

    • Jones, Julia Alexis, Ph.D.  candidate, 2019 -
    • Wang, Justin James, Ph.D.  candidate, 2019 -
    • He, Weiwei, Ph.D.  candidate, 2008 - 2013
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Background

education and training

  • Ph.D. in Biophysics and Computational Biology, University of Illinois at Urbana-Champaign 2000
  • B.S. in Biomedical Engineering, Capital Medical University 1993
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Contact

full name

  • Xiang-Lei Yang

geographic location

  • Scripps California 

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