Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Nucleolar GTPase NOG-1 Regulates Development, Fat Storage, and Longevity through Insulin/IGF Signaling in C. elegans

  • Kim, Young-Il (Biomedical Research Center, Korea Advanced Institute of Science and Technology) ;
  • Bandyopadhyay, Jaya (Department of Biotechnology, West Bengal University of Technology) ;
  • Cho, Injeong (Department of Biology Education, College of Education, Chosun University) ;
  • Lee, Juyeon (Department of Life Science, Gwangju Institute of Science and Technology) ;
  • Park, Dae Ho (Department of Life Science, Gwangju Institute of Science and Technology) ;
  • Cho, Jeong Hoon (Department of Biology Education, College of Education, Chosun University)
  • Received : 2013.09.09
  • Accepted : 2013.11.29
  • Published : 2014.01.31
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Abstract

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway.

Keywords

References

  1. Ashrafi, K. (2007). Obesity and the regulation of fat metabolism. In WormBook: The Online Review of C. elegans Biology, pp. 1-20.
  2. Ashrafi, K., Chang, F.Y., Watts, J.L., Fraser, A.G., Kamath, R.S., Ahringer, J., and Ruvkun, G. (2003). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268-272. https://doi.org/10.1038/nature01279
  3. Askjaer, P., Galy, V., Hannak, E., and Mattaj, I.W. (2002). Ran GTPase cycle and importins alpha and beta are essential for spindle formation and nuclear envelope assembly in living Caenorhabditis elegans embryos. Mol. Biol. Cell 13, 4355-4370. https://doi.org/10.1091/mbc.E02-06-0346
  4. Bamps, S., Wirtz, J., Savory, F.R., Lake, D., and Hope, I.A. (2009). The Caenorhabditis elegans sirtuin gene, sir-2.1, is widely expressed and induced upon caloric restriction. Mech. Age. Dev. 130, 762-770. https://doi.org/10.1016/j.mad.2009.10.001
  5. Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
  6. Buglino, J., Shen, V., Hakimian, P., and Lima, C.D. (2002), Structural and biochemical analysis of the Obg GTP binding protein. Structure 10, 1581-1592. https://doi.org/10.1016/S0969-2126(02)00882-1
  7. Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvari, M., Piper, M.D., Hoddinott, M., Sutphin, G.L., Leko, V., McElwee, J.J., et al. (2011). Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477, 482-485. https://doi.org/10.1038/nature10296
  8. Claypool, J.A., French, S.L., Johzuka, K., Eliason, K., Vu, L., Dodd, J.A., Beyer, A.L., and Nomura, M. (2004). Tor pathway regulates Rrn3p-dependent recruitment of yeast RNA polymerase I to the promoter but does not participate in alteration of the number of active genes. Mol. Biol. Cell 15, 946-956.
  9. Fromont-Racine, M., Senger, B., Saveanu, C., and Fasiolo, F. (2003). Ribosome assembly in eukaryotes. Gene 313, 17-42. https://doi.org/10.1016/S0378-1119(03)00629-2
  10. Fuentes, J.L., Datta, K., Sullivan, S.M., Walker, A., and Maddock, J.R. (2007). In vivo functional characterization of the Saccharomyces cerevisiae 60S biogenesis GTPase Nog1. Mol. Genet. Genomics 278, 105-123. https://doi.org/10.1007/s00438-007-0233-1
  11. Hannan, K.M., Brandenburger, Y., Jenkins, A., Sharkey, K., Cavanaugh, A., Rothblum, L., Moss, T., Poortinga, G., McArthur, G.A., Pearson, R.B., et al. (2003). mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol. Biol. Cell 23, 8862-8877. https://doi.org/10.1128/MCB.23.23.8862-8877.2003
  12. Hansen, M., Taubert, S., Crawford, D., Libina, N., Lee, S.J., and Kenyon, C. (2007). Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6, 95-110. https://doi.org/10.1111/j.1474-9726.2006.00267.x
  13. Harnpicharnchai, P., Jakovljevic, J., Horsey, E., Miles, T., Roman, J., Rout, M., Meagher, D., Imai, B., Guo, Y., Brame, C.J., et al. (2001). Composition and functional characterization of yeast 66S ribosome assembly intermediates. Mol. Cell 8, 505-515. https://doi.org/10.1016/S1097-2765(01)00344-6
  14. Honma, Y., Kitamura, A., Shioda, R., Maruyama, H., Ozaki, K., Oda, Y., Mini, T., Jeno, P., Maki, Y., Yonezawa, K., et al. (2006). TOR regulates late steps of ribosome maturation in the nucleoplasm via Nog1 in response to nutrients. EMBO J. 25, 3832-3842. https://doi.org/10.1038/sj.emboj.7601262
  15. Huh, W.K., Falvo, J.V., Gerke, L.C., Carroll, A.S., Howson, R.W., Weissman, J.S., and O'Shea, E.K. (2003). Global analysis of protein localization in budding yeast. Nature 425, 686-691. https://doi.org/10.1038/nature02026
  16. Jensen, B.C., Wang, Q., Kifer, C.T., and Parsons, M. (2003). The NOG1 GTP-binding protein is required for biogenesis of the 60 S ribosomal subunit. J. Biol. Chem. 278, 32204-32211. https://doi.org/10.1074/jbc.M304198200
  17. Jensen, B.C., Brekken, D.L., Randall, A.C., Kifer, C.T., and Parsons, M. (2005). Species specificity in ribosome biogenesis: a nonconserved phosphoprotein is required for formation of the large ribosomal subunit in Trypanosoma brucei. Eukaryotic Cell 4, 30-35. https://doi.org/10.1128/EC.4.1.30-35.2005
  18. Jia, K., Chen, D., and Riddle, D.L. (2004). The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131, 3897-3906. https://doi.org/10.1242/dev.01255
  19. Kenyon, C., Chang, J., Gensch, E., Rudner, A., and Tabtiang, R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464. https://doi.org/10.1038/366461a0
  20. Kimura, K.D., Tissenbaum, H.A., Liu, Y., and Ruvkun, G. (1997). daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946. https://doi.org/10.1126/science.277.5328.942
  21. Kressler, D., Linder, P., and de La Cruz, J. (1999). Protein transacting factors involved in ribosome biogenesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 19, 7897-7912. https://doi.org/10.1128/MCB.19.12.7897
  22. Kutay, U., Lipowsky, G., Izaurralde, E., Bischoff, F.R., Schwarzmaier, P., Hartmann, E., and Gorlich, D. (1998). Identification of a tRNA-specific nuclear export receptor. Mol. Cell 1, 359-369. https://doi.org/10.1016/S1097-2765(00)80036-2
  23. Lafontaine, D.L., and Tollervey, D. (2001). The function and synthesis of ribosomes. Nat. Rev. Mol. Cell. Biol. 2, 514-520. https://doi.org/10.1038/35080045
  24. Lapik, Y.R., Misra, J.M., Lau, L.F., and Pestov, D.G. (2007). Restricting conformational flexibility of the switch II region creates a dominant-inhibitory phenotype in Obg GTPase Nog1. Mol. Cell. Biol. 27, 7735-7744. https://doi.org/10.1128/MCB.01161-07
  25. Laping, N.J., Olson, B.A., and Zhu, Y. (2001). Identification of a novel nuclear guanosine triphosphate-binding protein differentially expressed in renal disease. J. Am. Soc. Neph. 12, 883-890.
  26. Lundquist, E.A. (2006). Small GTPases. In WormBook: The Online Review of C. elegans Biology, pp. 1-18.
  27. Mak, H.Y. (2012). Lipid droplets as fat storage organelles in Caenorhabditis elegans: thematic review series: lipid droplet synthesis and metabolism: from yeast to man. J. Lipid Res. 53, 28-33. https://doi.org/10.1194/jlr.R021006
  28. Marchler-Bauer, A., Zheng, C., Chitsaz, F., Derbyshire, M.K., Geer, L.Y., Geer, R.C., Gonzales, N.R., Gwadz, M., Hurwitz, D.I., Lanczycki, C.J., et al. (2013). CDD: conserved domains and protein three-dimensional structure. Nucleic Acids Res. 41, D348-352. https://doi.org/10.1093/nar/gks1243
  29. Mayer, C., and Grummt, I. (2006). Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases. Oncogene 25, 6384-6391. https://doi.org/10.1038/sj.onc.1209883
  30. Mello, C., and Fire, A. (1995). DNA transformation. Methods Cell Biol. 48, 451-482. https://doi.org/10.1016/S0091-679X(08)61399-0
  31. Moy, T.I., and Silver, P.A. (1999). Nuclear export of the small ribosomal subunit requires the ran-GTPase cycle and certain nucleoporins. Genes Dev. 13, 2118-2133. https://doi.org/10.1101/gad.13.16.2118
  32. Mukhopadhyay, A., Deplancke, B., Walhout, A.J., and Tissenbaum, H.A. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab. 2, 35-42. https://doi.org/10.1016/j.cmet.2005.06.004
  33. Ogg, S., Paradis, S., Gottlieb, S., Patterson, G.I., Lee, L., Tissenbaum, H.A., and Ruvkun, G. (1997). The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994-999. https://doi.org/10.1038/40194
  34. Oldham, S., and Hafen, E. (2003). Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 13, 79-85. https://doi.org/10.1016/S0962-8924(02)00042-9
  35. Pan, K.Z., Palter, J.E., Rogers, A.N., Olsen, A., Chen, D., Lithgow, G.J., and Kapahi, P. (2007). Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6, 111-119. https://doi.org/10.1111/j.1474-9726.2006.00266.x
  36. Powers, T., and Walter, P. (1999). Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol. Biol. Cell 10, 987-1000. https://doi.org/10.1091/mbc.10.4.987
  37. Saveanu, C., Namane, A., Gleizes, P.E., Lebreton, A., Rousselle, J.C., Noaillac-Depeyre, J., Gas, N., Jacquier, A., and Fromont-Racine, M. (2003). Sequential protein association with nascent 60S ribosomal particles. Mol. Cell. Biol. 23, 4449-4460. https://doi.org/10.1128/MCB.23.13.4449-4460.2003
  38. Schmelzle, T., and Hall, M.N. (2000). TOR, a central controller of cell growth. Cell 103, 253-262. https://doi.org/10.1016/S0092-8674(00)00117-3
  39. Steffen, K.K., MacKay, V.L., Kerr, E.O., Tsuchiya, M., Hu, D., Fox, L.A., Dang, N., Johnston, E.D., Oakes, J.A., Tchao, B.N., et al. (2008). Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell 133, 292-302. https://doi.org/10.1016/j.cell.2008.02.037
  40. Tsang, C.K., Bertram, P.G., Ai, W., Drenan, R., and Zheng, X.F. (2003). Chromatin-mediated regulation of nucleolar structure and RNA Pol I localization by TOR. EMBO J. 22, 6045-6056. https://doi.org/10.1093/emboj/cdg578
  41. Tschochner, H., and Hurt, E. (2003). Pre-ribosomes on the road from the nucleolus to the cytoplasm. Trends Cell Biol. 13, 255-263. https://doi.org/10.1016/S0962-8924(03)00054-0
  42. Urban, A., Neukirchen, S., and Jaeger, K. E. (1997). A rapid and efficient method for site-directed mutagenesis using one-step overlap extension PCR. Nucleic Acids Res. 25, 2227-2228. https://doi.org/10.1093/nar/25.11.2227
  43. Viswanathan, M., Kim, S.K., Berdichevsky, A., and Guarente, L. (2005). A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev. Cell 9:605-615. https://doi.org/10.1016/j.devcel.2005.09.017
  44. Venema, J., and Tollervey, D. (1999). Ribosome synthesis in Saccharomyces cerevisiae. Ann. Rev. Genet. 33, 261-311. https://doi.org/10.1146/annurev.genet.33.1.261
  45. Yang, J.S., Nam, H.J., Seo, M., Han, S.K., Choi, Y., Nam, H.G., Lee, S.J., and Kim, S. (2011). OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS One 6, e23525. https://doi.org/10.1371/journal.pone.0023525
  46. Yen, K., Le, T.T., Bansal, A., Narasimhan, S.D., Cheng, J.X., and Tissenbaum, H.A. (2010). A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS One 5, e12810. https://doi.org/10.1371/journal.pone.0012810
  47. Yudin, D., and Fainzilber, M. (2009). Ran on tracks--cytoplasmic roles for a nuclear regulator. J. Cell Sci. 122, 587-593. https://doi.org/10.1242/jcs.015289

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