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Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria


Autoři: Dae-Eun Jeong aff001;  Yujin Lee aff002;  Seokjin Ham aff002;  Dongyeop Lee aff001;  Sujeong Kwon aff002;  Hae-Eun H. Park aff002;  Sun-Young Hwang aff001;  Joo-Yeon Yoo aff001;  Tae-Young Roh aff001;  Seung-Jae V. Lee aff002
Působiště autorů: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea aff001;  Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-Gu, Daejeon, South Korea aff002
Vyšlo v časopise: Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008617
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008617

Souhrn

The oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity, and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of the OST complex remains incompletely understood. Here we show that the OST complex in C. elegans is crucial for ER protein homeostasis and defense against infection with pathogenic bacteria Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase. We found that genetic inhibition of the OST complex impaired protein processing in the ER, which in turn up-regulated ER unfolded protein response (UPRER). We identified vitellogenin VIT-6 as an OST-dependent glycosylated protein, critical for maintaining survival on PA14. We also showed that the OST complex was required for up-regulation of PMK-1 signaling upon infection with PA14. Our study demonstrates that an evolutionarily conserved OST complex, crucial for ER homeostasis, regulates host defense mechanisms against pathogenic bacteria.

Klíčová slova:

Bacterial pathogens – Caenorhabditis elegans – DNA transcription – Endoplasmic reticulum – Gene expression – Immunity – RNA interference – Transcription factors


Zdroje

1. Roth J, Zuber C, Park S, Jang I, Lee Y, Kysela KG, et al. Protein N-glycosylation, protein folding, and protein quality control. Mol Cells. 2010;30(6):497–506. Epub 2011/02/23. doi: 10.1007/s10059-010-0159-z 21340671.

2. Aebi M. N-linked protein glycosylation in the ER. Biochim Biophys Acta. 2013;1833(11):2430–7. Epub 2013/04/16. doi: 10.1016/j.bbamcr.2013.04.001 23583305.

3. Xu C, Ng DT. Glycosylation-directed quality control of protein folding. Nat Rev Mol Cell Biol. 2015;16(12):742–52. Epub 2015/10/16. doi: 10.1038/nrm4073 26465718.

4. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126(5):855–67. Epub 2006/09/09. doi: 10.1016/j.cell.2006.08.019 16959566.

5. Marth JD, Grewal PK. Mammalian glycosylation in immunity. Nat Rev Immunol. 2008;8(11):874–87. Epub 2008/10/11. doi: 10.1038/nri2417 18846099; PubMed Central PMCID: PMC2768770.

6. Lyons JJ, Milner JD, Rosenzweig SD. Glycans Instructing Immunity: The Emerging Role of Altered Glycosylation in Clinical Immunology. Front Pediatr. 2015;3:54. Epub 2015/07/01. doi: 10.3389/fped.2015.00054 26125015; PubMed Central PMCID: PMC4463932.

7. Monticelli M, Ferro T, Jaeken J, Dos Reis Ferreira V, Videira PA. Immunological aspects of congenital disorders of glycosylation (CDG): a review. J Inherit Metab Dis. 2016;39(6):765–80. Epub 2016/07/10. doi: 10.1007/s10545-016-9954-9 27393411.

8. Schwarz F, Aebi M. Mechanisms and principles of N-linked protein glycosylation. Curr Opin Struct Biol. 2011;21(5):576–82. Epub 2011/10/08. doi: 10.1016/j.sbi.2011.08.005 21978957.

9. Kelleher DJ, Gilmore R. An evolving view of the eukaryotic oligosaccharyltransferase. Glycobiology. 2006;16(4):47R–62R. Epub 2005/12/01. doi: 10.1093/glycob/cwj066 16317064.

10. Mohorko E, Glockshuber R, Aebi M. Oligosaccharyltransferase: the central enzyme of N-linked protein glycosylation. J Inherit Metab Dis. 2011;34(4):869–78. Epub 2011/05/27. doi: 10.1007/s10545-011-9337-1 21614585.

11. Stevens J, Spang A. N-glycosylation is required for secretion and mitosis in C. elegans. PLoS One. 2013;8(5):e63687. Epub 2013/05/22. doi: 10.1371/journal.pone.0063687 23691084; PubMed Central PMCID: PMC3653792.

12. Kaji H, Kamiie J, Kawakami H, Kido K, Yamauchi Y, Shinkawa T, et al. Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis elegans and suggests an atypical translocation mechanism for integral membrane proteins. Mol Cell Proteomics. 2007;6(12):2100–9. Epub 2007/09/01. doi: 10.1074/mcp.M600392-MCP200 17761667.

13. Zielinska DF, Gnad F, Schropp K, Wisniewski JR, Mann M. Mapping N-glycosylation sites across seven evolutionarily distant species reveals a divergent substrate proteome despite a common core machinery. Mol Cell. 2012;46(4):542–8. Epub 2012/05/29. doi: 10.1016/j.molcel.2012.04.031 22633491.

14. Irazoqui JE, Urbach JM, Ausubel FM. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol. 2010;10(1):47–58. Epub 2009/12/24. doi: 10.1038/nri2689 20029447; PubMed Central PMCID: PMC2965059.

15. Cohen LB, Troemel ER. Microbial pathogenesis and host defense in the nematode C. elegans. Curr Opin Microbiol. 2015;23:94–101. Epub 2014/12/03. doi: 10.1016/j.mib.2014.11.009 25461579; PubMed Central PMCID: PMC4324121.

16. Ewbank JJ, Pujol N. Local and long-range activation of innate immunity by infection and damage in C. elegans. Curr Opin Immunol. 2016;38:1–7. Epub 2015/10/31. doi: 10.1016/j.coi.2015.09.005 26517153.

17. Garsin DA, Sifri CD, Mylonakis E, Qin X, Singh KV, Murray BE, et al. A simple model host for identifying Gram-positive virulence factors. Proc Natl Acad Sci U S A. 2001;98(19):10892–7. Epub 2001/09/06. doi: 10.1073/pnas.191378698 11535834; PubMed Central PMCID: PMC58570.

18. Kim DH, Ewbank JJ. Signaling in the innate immune response. WormBook. 2018;2018:1–35. Epub 2015/12/24. doi: 10.1895/wormbook.1.83.2 26694508; PubMed Central PMCID: PMC6369418.

19. Hoffman C, Aballay A. Role of neurons in the control of immune defense. Curr Opin Immunol. 2019;60:30–6. Epub 2019/05/23. doi: 10.1016/j.coi.2019.04.005 31117013; PubMed Central PMCID: PMC6800625.

20. Felix MA, Duveau F. Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae. BMC Biol. 2012;10:59. Epub 2012/06/27. doi: 10.1186/1741-7007-10-59 22731941; PubMed Central PMCID: PMC3414772.

21. Shapira M. Host-microbiota interactions in Caenorhabditis elegans and their significance. Curr Opin Microbiol. 2017;38:142–7. Epub 2017/06/18. doi: 10.1016/j.mib.2017.05.012 28623729.

22. Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science. 2002;297(5581):623–6. Epub 2002/07/27. doi: 10.1126/science.1073759 12142542.

23. Shapira M, Hamlin BJ, Rong J, Chen K, Ronen M, Tan MW. A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci U S A. 2006;103(38):14086–91. Epub 2006/09/14. doi: 10.1073/pnas.0603424103 16968778; PubMed Central PMCID: PMC1599916.

24. Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, Kim DH. p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet. 2006;2(11):e183. Epub 2006/11/14. doi: 10.1371/journal.pgen.0020183 17096597; PubMed Central PMCID: PMC1635533.

25. Shivers RP, Pagano DJ, Kooistra T, Richardson CE, Reddy KC, Whitney JK, et al. Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS Genet. 2010;6(4):e1000892. Epub 2010/04/07. doi: 10.1371/journal.pgen.1000892 20369020; PubMed Central PMCID: PMC2848548.

26. Papp D, Csermely P, Soti C. A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. PLoS Pathog. 2012;8(4):e1002673. Epub 2012/05/12. doi: 10.1371/journal.ppat.1002673 22577361; PubMed Central PMCID: PMC3343120.

27. Block DH, Twumasi-Boateng K, Kang HS, Carlisle JA, Hanganu A, Lai TY, et al. The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans. PLoS Genet. 2015;11(5):e1005265. Epub 2015/05/29. doi: 10.1371/journal.pgen.1005265 26016853; PubMed Central PMCID: PMC4446034.

28. Fletcher M, Tillman EJ, Butty VL, Levine SS, Kim DH. Global transcriptional regulation of innate immunity by ATF-7 in C. elegans. PLoS Genet. 2019;15(2):e1007830. Epub 2019/02/23. doi: 10.1371/journal.pgen.1007830 30789901; PubMed Central PMCID: PMC6400416.

29. Richardson CE, Kooistra T, Kim DH. An essential role for XBP-1 in host protection against immune activation in C. elegans. Nature. 2010;463(7284):1092–5. Epub 2010/02/26. doi: 10.1038/nature08762 20182512; PubMed Central PMCID: PMC2834299.

30. Richardson CE, Kinkel S, Kim DH. Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. PLoS Genet. 2011;7(11):e1002391. Epub 2011/11/30. doi: 10.1371/journal.pgen.1002391 22125500; PubMed Central PMCID: PMC3219621.

31. Dai LL, Gao JX, Zou CG, Ma YC, Zhang KQ. mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection. PLoS Pathog. 2015;11(1):e1004606. Epub 2015/01/09. doi: 10.1371/journal.ppat.1004606 25569229; PubMed Central PMCID: PMC4287614.

32. Jeong DE, Lee D, Hwang SY, Lee Y, Lee JE, Seo M, et al. Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling. EMBO J. 2017;36(8):1046–65. Epub 2017/03/12. doi: 10.15252/embj.201694781 28283579; PubMed Central PMCID: PMC5391144.

33. Igura M, Maita N, Kamishikiryo J, Yamada M, Obita T, Maenaka K, et al. Structure-guided identification of a new catalytic motif of oligosaccharyltransferase. EMBO J. 2008;27(1):234–43. Epub 2007/11/30. doi: 10.1038/sj.emboj.7601940 18046457; PubMed Central PMCID: PMC2206122.

34. Tan MW, Mahajan-Miklos S, Ausubel FM. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A. 1999;96(2):715–20. Epub 1999/01/20. doi: 10.1073/pnas.96.2.715 9892699; PubMed Central PMCID: PMC15202.

35. Tan MW, Rahme LG, Sternberg JA, Tompkins RG, Ausubel FM. Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc Natl Acad Sci U S A. 1999;96(5):2408–13. Epub 1999/03/03. doi: 10.1073/pnas.96.5.2408 10051655; PubMed Central PMCID: PMC26797.

36. Kirienko NV, Cezairliyan BO, Ausubel FM, Powell JR. Pseudomonas aeruginosa PA14 pathogenesis in Caenorhabditis elegans. Methods Mol Biol. 2014;1149:653–69. Epub 2014/05/14. doi: 10.1007/978-1-4939-0473-0_50 24818940.

37. Denzel MS, Storm NJ, Gutschmidt A, Baddi R, Hinze Y, Jarosch E, et al. Hexosamine pathway metabolites enhance protein quality control and prolong life. Cell. 2014;156(6):1167–78. Epub 2014/03/19. doi: 10.1016/j.cell.2014.01.061 24630720.

38. Hunt-Newbury R, Viveiros R, Johnsen R, Mah A, Anastas D, Fang L, et al. High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS Biol. 2007;5(9):e237. Epub 2007/09/14. doi: 10.1371/journal.pbio.0050237 17850180; PubMed Central PMCID: PMC1971126.

39. Singh J, Aballay A. Endoplasmic Reticulum Stress Caused by Lipoprotein Accumulation Suppresses Immunity against Bacterial Pathogens and Contributes to Immunosenescence. MBio. 2017;8(3). Epub 2017/06/01. doi: 10.1128/mBio.00778-17 28559483; PubMed Central PMCID: PMC5449662.

40. Yang W, Dierking K, Schulenburg H. WormExp: a web-based application for a Caenorhabditis elegans-specific gene expression enrichment analysis. Bioinformatics. 2016;32(6):943–5. Epub 2015/11/13. doi: 10.1093/bioinformatics/btv667 26559506.

41. Bond MR, Ghosh SK, Wang P, Hanover JA. Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity. PLoS One. 2014;9(12):e113231. Epub 2014/12/05. doi: 10.1371/journal.pone.0113231 25474640; PubMed Central PMCID: PMC4256294.

42. McEwan DL, Feinbaum RL, Stroustrup N, Haas W, Conery AL, Anselmo A, et al. Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway. BMC Biol. 2016;14(1):105. Epub 2016/12/09. doi: 10.1186/s12915-016-0334-6 27927200; PubMed Central PMCID: PMC5143455.

43. Mann FG, Van Nostrand EL, Friedland AE, Liu X, Kim SK. Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans. PLoS Genet. 2016;12(4):e1005956. Epub 2016/04/14. doi: 10.1371/journal.pgen.1005956 27070429; PubMed Central PMCID: PMC4829211.

44. Dineen A, Osborne Nishimura E, Goszczynski B, Rothman JH, McGhee JD. Quantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm. Dev Biol. 2018;435(2):150–61. Epub 2018/01/24. doi: 10.1016/j.ydbio.2017.12.023 29360433; PubMed Central PMCID: PMC6476323.

45. Estes KA, Dunbar TL, Powell JR, Ausubel FM, Troemel ER. bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2010;107(5):2153–8. Epub 2010/02/06. doi: 10.1073/pnas.0914643107 20133860; PubMed Central PMCID: PMC2836710.

46. Steinbaugh MJ, Narasimhan SD, Robida-Stubbs S, Moronetti Mazzeo LE, Dreyfuss JM, Hourihan JM, et al. Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence. Elife. 2015;4. Epub 2015/07/22. doi: 10.7554/eLife.07836 26196144; PubMed Central PMCID: PMC4541496.

47. Li J, Chauve L, Phelps G, Brielmann RM, Morimoto RI. E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response. Genes Dev. 2016;30(18):2062–75. Epub 2016/11/01. doi: 10.1101/gad.283317.116 27688402; PubMed Central PMCID: PMC5066613.

48. Zhang B, Xiao R, Ronan EA, He Y, Hsu AL, Liu J, et al. Environmental Temperature Differentially Modulates C. elegans Longevity through a Thermosensitive TRP Channel. Cell Rep. 2015;11(9):1414–24. Epub 2015/06/02. doi: 10.1016/j.celrep.2015.04.066 26027928; PubMed Central PMCID: PMC4758836.

49. Kim DH, Liberati NT, Mizuno T, Inoue H, Hisamoto N, Matsumoto K, et al. Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase. Proc Natl Acad Sci U S A. 2004;101(30):10990–4. Epub 2004/07/17. doi: 10.1073/pnas.0403546101 15256594; PubMed Central PMCID: PMC503731.

50. Singh V, Aballay A. Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci U S A. 2006;103(35):13092–7. Epub 2006/08/19. doi: 10.1073/pnas.0604050103 16916933; PubMed Central PMCID: PMC1559758.

51. Yang W, Dierking K, Rosenstiel PC, Schulenburg H. GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens. Zoology (Jena). 2016;119(4):244–53. Epub 2016/07/04. doi: 10.1016/j.zool.2016.05.013 27372411.

52. Bogaerts A, Beets I, Temmerman L, Schoofs L, Verleyen PJBD. Proteome changes of Caenorhabditis elegans upon a Staphylococcus aureus infection. 2010;5(1):11. doi: 10.1186/1745-6150-5-11 20163716

53. Dierking K, Yang W, Schulenburg H. Antimicrobial effectors in the nematode Caenorhabditis elegans: an outgroup to the Arthropoda. Philos Trans R Soc Lond B Biol Sci. 2016;371(1695). Epub 2016/05/11. doi: 10.1098/rstb.2015.0299 27160601; PubMed Central PMCID: PMC4874396.

54. Grant B, Hirsh D. Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol Biol Cell. 1999;10(12):4311–26. Epub 1999/12/10. doi: 10.1091/mbc.10.12.4311 10588660; PubMed Central PMCID: PMC25760.

55. Lee SH, Omi S, Thakur N, Taffoni C, Belougne J, Engelmann I, et al. Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans. Virulence. 2018;9(1):648–58. Epub 2018/02/07. doi: 10.1080/21505594.2018.1433969 29405821; PubMed Central PMCID: PMC5955453.

56. Ezcurra M, Benedetto A, Sornda T, Gilliat AF, Au C, Zhang Q, et al. C. elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent Pathologies. Curr Biol. 2018;28(20):3352. Epub 2018/10/24. doi: 10.1016/j.cub.2018.10.003 30352178; PubMed Central PMCID: PMC6203452.

57. Akiyoshi S, Nomura KH, Dejima K, Murata D, Matsuda A, Kanaki N, et al. RNAi screening of human glycogene orthologs in the nematode Caenorhabditis elegans and the construction of the C. elegans glycogene database. Glycobiology. 2015;25(1):8–20. Epub 2014/08/06. doi: 10.1093/glycob/cwu080 25091817; PubMed Central PMCID: PMC4245905.

58. Urano F, Calfon M, Yoneda T, Yun C, Kiraly M, Clark SG, et al. A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol. 2002;158(4):639–46. Epub 2002/08/21. doi: 10.1083/jcb.200203086 12186849; PubMed Central PMCID: PMC2174003.

59. Haskins KA, Russell JF, Gaddis N, Dressman HK, Aballay A. Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity. Dev Cell. 2008;15(1):87–97. Epub 2008/07/09. doi: 10.1016/j.devcel.2008.05.006 18606143; PubMed Central PMCID: PMC2517226.

60. Sun J, Singh V, Kajino-Sakamoto R, Aballay A. Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science. 2011;332(6030):729–32. Epub 2011/04/09. doi: 10.1126/science.1203411 21474712; PubMed Central PMCID: PMC3125668.

61. Parnas O, Jovanovic M, Eisenhaure TM, Herbst RH, Dixit A, Ye CJ, et al. A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks. Cell. 2015;162(3):675–86. Epub 2015/07/21. doi: 10.1016/j.cell.2015.06.059 26189680; PubMed Central PMCID: PMC4522370.

62. Sun J, Duffy KE, Ranjith-Kumar CT, Xiong J, Lamb RJ, Santos J, et al. Structural and functional analyses of the human Toll-like receptor 3. Role of glycosylation. J Biol Chem. 2006;281(16):11144–51. Epub 2006/03/15. doi: 10.1074/jbc.M510442200 16533755.

63. Komura T, Sakai Y, Honda M, Takamura T, Wada T, Kaneko S. ER stress induced impaired TLR signaling and macrophage differentiation of human monocytes. Cell Immunol. 2013;282(1):44–52. Epub 2013/05/15. doi: 10.1016/j.cellimm.2013.04.006 23665674.

64. Van den Steen P, Rudd PM, Dwek RA, Van Damme J, Opdenakker G. Cytokine and Protease Glycosylation as a Regulatory Mechanism in Inflammation and Autoimmunity. In: Axford JS, editor. Glycoimmunology 2. Boston, MA: Springer US; 1998. p. 133–43.

65. Stiernagle T. Maintenance of C. elegans. WormBook. 2006:1–11. Epub 2007/12/01. doi: 10.1895/wormbook.1.101.1 18050451; PubMed Central PMCID: PMC4781397.

66. Reddy KC, Andersen EC, Kruglyak L, Kim DH. A polymorphism in npr-1 is a behavioral determinant of pathogen susceptibility in C. elegans. Science. 2009;323(5912):382–4. Epub 2009/01/20. doi: 10.1126/science.1166527 19150845; PubMed Central PMCID: PMC2748219.

67. Tan MW. Identification of host and pathogen factors involved in virulence using Caenorhabditis elegans. Methods Enzymol. 2002;358:13–28. Epub 2002/12/12. doi: 10.1016/s0076-6879(02)58078-2 12474376.

68. Hwang AB, Ryu EA, Artan M, Chang HW, Kabir MH, Nam HJ, et al. Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2014;111(42):E4458–67. Epub 2014/10/08. doi: 10.1073/pnas.1411199111 25288734; PubMed Central PMCID: PMC4210294.

69. Yang JS, Nam HJ, Seo M, Han SK, Choi Y, Nam HG, et al. OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS One. 2011;6(8):e23525. Epub 2011/08/23. doi: 10.1371/journal.pone.0023525 21858155; PubMed Central PMCID: PMC3156233.

70. Han SK, Lee D, Lee H, Kim D, Son HG, Yang JS, et al. OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research. Oncotarget. 2016;7(35):56147–52. Epub 2016/08/17. doi: 10.18632/oncotarget.11269 27528229; PubMed Central PMCID: PMC5302902.

71. Lee D, Jeong DE, Son HG, Yamaoka Y, Kim H, Seo K, et al. SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat. Genes Dev. 2015;29(23):2490–503. Epub 2015/12/08. doi: 10.1101/gad.266304.115 26637528; PubMed Central PMCID: PMC4691952.

72. Seo K, Choi E, Lee D, Jeong DE, Jang SK, Lee SJ. Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 2013;12(6):1073–81. Epub 2013/07/25. doi: 10.1111/acel.12140 23879233.

73. Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12(4):357–60. Epub 2015/03/10. doi: 10.1038/nmeth.3317 25751142; PubMed Central PMCID: PMC4655817.

74. Pertea M, Pertea GM, Antonescu CM, Chang TC, Mendell JT, Salzberg SL. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol. 2015;33(3):290–5. Epub 2015/02/19. doi: 10.1038/nbt.3122 25690850; PubMed Central PMCID: PMC4643835.

75. Frazee AC, Pertea G, Jaffe AE, Langmead B, Salzberg SL, Leek JT. Ballgown bridges the gap between transcriptome assembly and expression analysis. Nat Biotechnol. 2015;33(3):243–6. Epub 2015/03/10. doi: 10.1038/nbt.3172 25748911; PubMed Central PMCID: PMC4792117.

76. Risso D, Ngai J, Speed TP, Dudoit S. Normalization of RNA-seq data using factor analysis of control genes or samples. Nat Biotechnol. 2014;32(9):896–902. Epub 2014/08/26. doi: 10.1038/nbt.2931 25150836; PubMed Central PMCID: PMC4404308.

77. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. Epub 2014/12/18. doi: 10.1186/s13059-014-0550-8 25516281; PubMed Central PMCID: PMC4302049.

78. Falcon S, Gentleman R. Using GOstats to test gene lists for GO term association. Bioinformatics. 2007;23(2):257–8. Epub 2006/11/14. doi: 10.1093/bioinformatics/btl567 17098774.

79. Katz Y, Wang ET, Airoldi EM, Burge CB. Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat Methods. 2010;7(12):1009–15. Epub 2010/11/09. doi: 10.1038/nmeth.1528 21057496; PubMed Central PMCID: PMC3037023.

80. McLeay RC, Bailey TL. Motif Enrichment Analysis: a unified framework and an evaluation on ChIP data. BMC Bioinformatics. 2010;11:165. Epub 2010/04/02. doi: 10.1186/1471-2105-11-165 20356413; PubMed Central PMCID: PMC2868005.

81. Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, et al. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res. 2018;46(D1):D260–D6. Epub 2017/11/16. doi: 10.1093/nar/gkx1126 29140473; PubMed Central PMCID: PMC5753243.

82. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50. Epub 2005/10/04. doi: 10.1073/pnas.0506580102 16199517; PubMed Central PMCID: PMC1239896.

83. Dillin A, Hsu AL, Arantes-Oliveira N, Lehrer-Graiwer J, Hsin H, Fraser AG, et al. Rates of behavior and aging specified by mitochondrial function during development. Science. 2002;298(5602):2398–401. Epub 2002/12/10. doi: 10.1126/science.1077780 12471266.


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