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Methionyl-tRNA Synthetase Regulates Lifespan in Drosophila

  • Suh, Yoon Seok (Metabolism and Neurophysiology Research Group, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Yeom, Eunbyul (Metabolism and Neurophysiology Research Group, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Nam, Jong-Woo (Department of Biological Sciences, Inha University) ;
  • Min, Kyung-Jin (Department of Biological Sciences, Inha University) ;
  • Lee, Jeongsoo (Metabolism and Neurophysiology Research Group, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Yu, Kweon (Metabolism and Neurophysiology Research Group, Korea Research Institute of Bioscience & Biotechnology (KRIBB))
  • Received : 2019.11.15
  • Accepted : 2019.12.18
  • Published : 2020.03.31

Abstract

Methionyl-tRNA synthetase (MRS) is essential for translation. MRS mutants reduce global translation, which usually increases lifespan in various genetic models. However, we found that MRS inhibited Drosophila reduced lifespan despite of the reduced protein synthesis. Microarray analysis with MRS inhibited Drosophila revealed significant changes in inflammatory and immune response genes. Especially, the expression of anti-microbial peptides (AMPs) genes was reduced. When we measured the expression levels of AMP genes during aging, those were getting increased in the control flies but reduced in MRS inhibition flies age-dependently. Interestingly, in the germ-free condition, the maximum lifespan was increased in MRS inhibition flies compared with that of the conventional condition. These findings suggest that the lifespan of MRS inhibition flies is reduced due to the down-regulated AMPs expression in Drosophila.

Keywords

References

  1. Badinloo, M., Nguyen, E., Suh, W., Alzahrani, F., Castellanos, J., Klichko, V.I., Orr, W.C., and Radyuk, S.N. (2018). Overexpression of antimicrobial peptides contributes to aging through cytotoxic effects in Drosophila tissues. Arch. Insect Biochem. Physiol. 98, e21464. https://doi.org/10.1002/arch.21464
  2. Barcena, C., Quiros, P.M., Durand, S., Mayoral, P., Rodriguez, F., Caravia, X.M., Marino, G., Garabaya, C., Fernandez-Garcia, M.T., Kroemer, G., et al. (2018). Methionine restriction extends lifespan in progeroid mice and alters lipid and bile acid metabolism. Cell Rep. 24, 2392-2403. https://doi.org/10.1016/j.celrep.2018.07.089
  3. Becker, T., Loch, G., Beyer, M., Zinke, I., Aschenbrenner, A.C., Carrera, P., Inhester, T., Schultze, J.L., and Hoch, M. (2010). FOXO-dependent regulation of innate immune homeostasis. Nature 463, 369-373. https://doi.org/10.1038/nature08698
  4. Bjedov, I., Toivonen, J.M., Kerr, F., Slack, C., Jacobson, J., Foley, A., and Partridge, L. (2010). Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 11, 35-46. https://doi.org/10.1016/j.cmet.2009.11.010
  5. Broughton, S. and Partridge, L. (2009). Insulin/IGF-like signalling, the central nervous system and aging. Biochem. J. 418, 1-12. https://doi.org/10.1042/BJ20082102
  6. Brummel, T., Ching, A., Seroude, L., Simon, A.F., and Benzer, S. (2004). Drosophila lifespan enhancement by exogenous bacteria. Proc. Natl. Acad. Sci. U. S. A. 101, 12974-12979. https://doi.org/10.1073/pnas.0405207101
  7. Edwards, C., Canfield, J., Copes, N., Brito, A., Rehan, M., Lipps, D., Brunquell, J., Westerheide, S.D., and Bradshaw, P.C. (2015). Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genet. 16, 8. https://doi.org/10.1186/s12863-015-0167-2
  8. Eisler, H., Frohlich, K.U., and Heidenreich, E. (2004). Starvation for an essential amino acid induces apoptosis and oxidative stress in yeast. Exp. Cell Res. 300, 345-353. https://doi.org/10.1016/j.yexcr.2004.07.025
  9. Fabian, D.K., Garschall, K., Klepsatel, P., Santos-Matos, G., Sucena, E., Kapun, M., Lemaitre, B., Schlotterer, C., Arking, R., and Flatt, T. (2018). Evolution of longevity improves immunity in Drosophila. Evol. Lett. 2, 567-579. https://doi.org/10.1002/evl3.89
  10. Fullerton, M.D. and Steinberg, G.R. (2010). SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol. Diabetes 59, 551-553. https://doi.org/10.2337/db09-1732
  11. Han, J.M., Jeong, S.J., Park, M.C., Kim, G., Kwon, N.H., Kim, H.K., Ha, S.H., Ryu, S.H., and Kim, S. (2012). Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149, 410-424. https://doi.org/10.1016/j.cell.2012.02.044
  12. Han, J.M., Lee, M.J., Park, S.G., Lee, S.H., Razin, E., Choi, E.C., and Kim, S. (2006). Hierarchical network between the components of the multi-tRNA synthetase complex: Implications for complex formation. J. Biol. Chem. 281, 38663-38667. https://doi.org/10.1074/jbc.M605211200
  13. Han, S.K., Lee, D., Lee, H., Kim, D., Son, H.G., Yang, J.S., Lee, S.J.V., and Kim, S. (2016). OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research. Oncotarget 7, 56147-56152. https://doi.org/10.18632/oncotarget.11269
  14. Hoffmann, J.A. (2003). The immune response of Drosophila. Nature 426, 33-38. https://doi.org/10.1038/nature02021
  15. Ikeya, T., Galic, M., Belawat, P., Nairz, K., and Hafen, E. (2002). Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Curr. Biol. 12, 1293-1300. https://doi.org/10.1016/S0960-9822(02)01043-6
  16. Kapahi, P., Kaeberlein, M., and Hansen, M. (2017). Dietary restriction and lifespan: lessons from invertebrate models. Ageing Res. Rev. 39, 3-14. https://doi.org/10.1016/j.arr.2016.12.005
  17. Kapahi, P., Zid, B.M., Harper, T., Koslover, D., Sapin, V., and Benzer, S. (2004). Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885-890. https://doi.org/10.1016/j.cub.2004.03.059
  18. Khan, S. (2016). Recent advances in the biology and drug targeting of malaria parasite aminoacyl-tRNA synthetases. Malar. J. 15, 203. https://doi.org/10.1186/s12936-016-1247-0
  19. Ko, Y.G., Kang, Y.S., Kim, E.K., Park, S.G., and Kim, S. (2000). Nucleolar localization of human methionyl-tRNA synthetase and its role in ribosomal RNA synthesis. J. Cell Biol. 149, 567-574. https://doi.org/10.1083/jcb.149.3.567
  20. Ko, Y.G., Park, H., Kim, T., Lee, J.W., Park, S.G., Seol, W., Kim, J.E., Lee, W.H., Kim, S.H., Park, J.E., et al. (2001). A cofactor of tRNA synthetase, p43, is secreted to up-regulate proinflammatory genes. J. Biol. Chem. 276, 23028-23033. https://doi.org/10.1074/jbc.M101544200
  21. Kuk, M.U., Kim, J.W., Lee, Y.S., Cho, K.A., Park, J.T., and Park, S.C. (2019). Alleviation of senescence via ATM inhibition in accelerated aging models. Mol. Cells 42, 210-217. https://doi.org/10.14348/molcells.2018.0352
  22. Lee, E.Y., Lee, H.C., Kim, H.K., Jang, S.Y., Park, S.J., Kim, Y.H., Kim, J.H., Hwang, J., Kim, J.H., Kim, T.H., et al. (2016). Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity. Nat. Immunol. 17, 1252-1262. https://doi.org/10.1038/ni.3542
  23. Lee, S.W., Cho, B.H., Park, S.G., and Kim, S. (2004). Aminoacyl-tRNA synthetase complexes: beyond translation. J. Cell Sci. 117, 3725-3734. https://doi.org/10.1242/jcs.01342
  24. Lemaitre, B., Reichhart, J.M., and Hoffmann, J.A. (1997). Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc. Natl. Acad. Sci. U. S. A. 94, 14614-14619. https://doi.org/10.1073/pnas.94.26.14614
  25. Liang, Y.R., Liu, C., Lu, M.Y., Dong, Q.Y., Wang, Z.M., Wang, Z.R., Xiong, W.X., Zhang, N.N., Zhou, J.W., Liu, Q.F., et al. (2018). Calorie restriction is the most reasonable anti-ageing intervention: a meta-analysis of survival curves. Sci. Rep. 8, 5779. https://doi.org/10.1038/s41598-018-24146-z
  26. Min, K.J. and Tatar, M. (2018). Unraveling the molecular mechanism of immunosenescence in Drosophila. Int. J. Mol. Sci. 19, E2472. https://doi.org/10.3390/ijms19092472
  27. Min, K.J., Yamamoto, R., Buch, S., Pankratz, M., and Tatar, M. (2008). Drosophila lifespan control by dietary restriction independent of insulinlike signaling. Aging Cell 7, 199-206. https://doi.org/10.1111/j.1474-9726.2008.00373.x
  28. Netzer, N., Goodenbour, J.M., David, A., Dittmar, K.A., Jones, R.B., Schneider, J.R., Boone, D., Eves, E.M., Rosner, M.R., Gibbs, J.S., et al. (2009). Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature 462, 522-526. https://doi.org/10.1038/nature08576
  29. Park, S.G., Kim, H.J., Min, Y.H., Choi, E.C., Shin, Y.K., Park, B.J., Lee, S.W., and Kim, S. (2005). Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc. Natl. Acad. Sci. U. S. A. 102, 6356-6361. https://doi.org/10.1073/pnas.0500226102
  30. Partridge, L., Piper, M.D., and Mair, W. (2005). Dietary restriction in Drosophila. Mech. Ageing Dev. 126, 938-950. https://doi.org/10.1016/j.mad.2005.03.023
  31. Petkau, K., Parsons, B.D., Duggal, A., and Foley, E. (2014). A deregulated intestinal cell cycle program disrupts tissue homeostasis without affecting longevity in Drosophila. J. Biol. Chem. 289, 28719-28729. https://doi.org/10.1074/jbc.M114.578708
  32. Schmidt, E.K., Clavarino, G., Ceppi, M., and Pierre, P. (2009). SUnSET, a nonradioactive method to monitor protein synthesis. Nat. Methods 6, 275-277. https://doi.org/10.1038/nmeth.1314
  33. Simpson, N.H., Singh, R.P., Perani, A., Goldenzon, C., and Al-Rubeai, M. (1998). In hybridoma cultures, deprivation of any single amino acid leads to apoptotic death, which is suppressed by the expression of the bcl-2 gene. Biotechnol. Bioeng. 59, 90-98. https://doi.org/10.1002/(SICI)1097-0290(19980705)59:1<90::AID-BIT12>3.0.CO;2-6
  34. Stoven, S., Ando, I., Kadalayil, L., Engstrom, Y., and Hultmark, D. (2000). Activation of the Drosophila NF-kappaB factor relish by rapid endoproteolytic cleavage. EMBO Rep. 1, 347-352. https://doi.org/10.1093/embo-reports/kvd072
  35. Tzatsos, A. and Kandror, K.V. (2006). Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol. Cell. Biol. 26, 63-76. https://doi.org/10.1128/MCB.26.1.63-76.2006
  36. Xiao, F., Huang, Z.Y., Li, H.K., Yu, J.J., Wang, C.X., Chen, S.H., Meng, Q.S., Cheng, Y., Gao, X.A., Li, J., et al. (2011). Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes 60, 746-756. https://doi.org/10.2337/db10-1246
  37. Zerofsky, M., Harel, E., Silverman, N., and Tatar, M. (2005). Aging of the innate immune response in Drosophila melanogaster. Aging Cell 4, 103-108. https://doi.org/10.1111/j.1474-9728.2005.00147.x

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