The UPR Branch IRE1- in Plants Plays an Essential Role in Viral Infection and Is Complementary to the Only UPR Pathway in Yeast

English version České info

The unfolded protein response (UPR) is crucial to life as it regulates gene expression in response to stress in the endoplasmic reticulum (ER). There are two functionally overlapping UPR branches in plants, e.g., IRE1-bZIP60 and S1P/S2P-bZIP17/bZIP28, but only one, IRE1p-HAC1, in yeast. Despite recent significant progress in understanding UPR, a functional connectivity of IRE1 and its splicing target has not been established in multicellular eukaryotes. It is unknown if a single UPR branch in plants has any unique biological functions. Given that all eukaryotes are equipped with the IRE1-mediated pathway, are IRE1 downstream signaling effectors conserved among kingdoms and at what degree? Here, we show that IRE1 and its substrate bZIP60 function as a matched enzyme-substrate pair to mediate virus-host interactions in plants. We further provide evidence that a single UPR branch, IRE1-bZIP60, rather than S1P/S2P-bZIP17/bZIP28, determines viral pathogenesis, indicating that the two UPR arms may have distinct functions in plants. Finally, we demonstrate that the spliced form bZIP60 and HAC1p, rather than IRE1, are functionally replaceable to cope with abiotic stress in yeast, suggesting that the downstream signaling of the IRE1-mediated splicing is evolutionary conserved in plants and yeast. These data shed new lights into UPR in multicellular eukaryotes.

Vyšlo v časopise: The UPR Branch IRE1- in Plants Plays an Essential Role in Viral Infection and Is Complementary to the Only UPR Pathway in Yeast. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005164
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005164

Souhrn

Zdroje

1. Chen Y, Brandizzi F (2013) IRE1: ER stress sensor and cell fate executor. Trends Cell Biol 23: 547–555. doi: 10.1016/j.tcb.2013.06.005 23880584

2. Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13: 89–102. doi: 10.1038/nrm3270 22251901

3. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334: 1081–1086. doi: 10.1126/science.1209038 22116877

4. Smith JA (2014) A new paradigm: innate immune sensing of viruses via the unfolded protein response. Front Microbiol 5: 222. doi: 10.3389/fmicb.2014.00222 24904537

5. Williams B, Verchot J, Dickman M (2014) When supply does not meet demand-ER stress and plant programmed cell death. Front Plant Sci 5: 211. doi: 10.3389/fpls.2014.00211 24926295

6. Wang J, Pareja KA, Kaiser CA, Sevier CS (2014) Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress. eLIFE 3: e03496. doi: 10.7554/eLife.03496 25053742

7. Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS, et al. (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101: 249–258.

8. Li H, Korennykh AV, Behrman SL, Walter P (2010) Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering. Proc Natl Acad Sci USA 107: 16113–16118. doi: 10.1073/pnas.1010580107 20798350

9. Shamu CE, Walter P (1996) Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J 15: 3028–3039. 8670804

10. Gardner BM, Walter P (2011) Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response. Science 333: 1891–1894.

11. Lee KP, Dey M, Neculai D, Cao C, Dever TE, et al. (2008) Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell 132: 89–100. doi: 10.1016/j.cell.2007.10.057 18191223

12. Cox JS, Walter P (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87: 391–404.

13. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, et al. (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP1 mRNA. Nature 415: 92–96. 11780124

14. Uemura A, Oku M, Mori K, Yoshida H (2009) Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the mammalian unfolded protein response. J Cell Sci 122: 2877–2886. doi: 10.1242/jcs.040584 19622636

15. Deng Y, Humbert S, Liu JX, Srivastava R, Rothstein SJ, et al. (2011) Heat induces the splicing by IRE1 of a mRNA encoding a transcription factor involved in the unfolded protein response in Arabidopsis. Proc Natl Acad Sci USA 108: 7247–7252. doi: 10.1073/pnas.1102117108 21482766

16. Zhang L, Wang A (2012) Virus-induced ER stress and the unfolded protein response. Front Plant Sci 3: 293. doi: 10.3389/fpls.2012.00293 23293645

17. Hetz C, Martinon F, Rodriguez D, Glimcher LH (2011) The unfolded protein response: integrating stress signals through the stress sensor IRE1α. Physiol Rev 91: 1219–1243. doi: 10.1152/physrev.00001.2011 22013210

18. Mori K, Ogawa N, Kawahara T, Yanagi H, Yura T (2000) mRNA splicing-mediated C-terminal replacement of transcription factor Hac1p is required for efficient activation of the unfolded protein response. Proc Natl Acad Sci USA 97: 4660–4665. 10781071

19. Yoshida H, Oku M, Suzuki M, Mori K (2006) pXBP1 (U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response activator pXBP1 (S) in mammalian ER stress response. J Cell Biol 172: 565–575.

20. Rüegsegger U, Leber JH, Walter P (2001) Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell 107: 103–114.

21. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, et al. (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318: 944–949. 17991856

22. Nagashima Y, Mishiba K-i, Suzuki E, Shimada Y, Iwata Y, et al. (2011) Arabidopsis IRE1 catalyses unconventional splicing of bZIP60 mRNA to produce the active transcription factor. Sci Rep 1: 29.

23. Liu JX, Howell SH (2010) bZIP28 and NF-Y transcription factors are activated by ER stress and assemble into a transcriptional complex to regulate stress response genes in Arabidopsis. Plant Cell 22: 782–796. doi: 10.1105/tpc.109.072173 20207753

24. Gao H, Brandizzi F, Benning C, Larkin RM (2008) A membrane-tethered transcription factor defines a branch of the heat stress response in Arabidopsis thaliana. Proc Natl Acad Sci USA 105: 16398–16403. doi: 10.1073/pnas.0808463105 18849477

25. Liu JX, Srivastava R, Che P, Howell SH (2007) Salt stress responses in Arabidopsis utilize a signal transduction pathway related to endoplasmic reticulum stress signaling. Plant J 51: 897–909.

26. Noh S-J, Kwon CS, Chung W (2002) Characterization of two homologs of Ire1p, a kinase/endoribonuclease in yeast, in Arabidopsis thaliana. Biochim Biophys Acta (BBA)-Gene Structure and Expression 1575: 130–134. 12020828

27. Koizumi N, Martinez IM, Kimata Y, Kohno K, Sano H, et al. (2001) Molecular characterization of two Arabidopsis Ire1 homologs, endoplasmic reticulum-located transmembrane protein kinases. Plant Physiol 127: 949–962. 11706177

28. Chen Y, Brandizzi F (2012) AtIRE1A/AtIRE1B and AGB1 independently control two essential unfolded protein response pathways in Arabidopsis. Plant J 69: 266–277. doi: 10.1111/j.1365-313X.2011.04788.x 21914012

29. Deng Y, Srivastava R, Howell SH (2013) Endoplasmic reticulum (ER) stress response and its physiological roles in plants. Int J Mol Sci 14: 8188–8212. doi: 10.3390/ijms14048188 23591838

30. Moreno AA, Mukhtar MS, Blanco F, Boatwright JL, Moreno I, et al. (2012) IRE1/bZIP60-mediated unfolded protein response plays distinct roles in plant immunity and abiotic stress responses. PLoS ONE 7: e31944. doi: 10.1371/journal.pone.0031944 22359644

31. Oikawa D, Tokuda M, Hosoda A, Iwawaki T (2010) Identification of a consensus element recognized and cleaved by IRE1α. Nucleic Acids Res 38: 6265–6273. doi: 10.1093/nar/gkq452 20507909

32. Gonzalez TN, Sidrauski C, Dörfler S, Walter P (1999) Mechanism of non-spliceosomal mRNA splicing in the unfolded protein response pathway. EMBO J 18: 3119–3132. 10357823

33. Howell SH (2013) Endoplasmic reticulum stress responses in plants. Annu Rev Plant Biol 64: 477–499. doi: 10.1146/annurev-arplant-050312-120053 23330794

34. Kimmig P, Diaz M, Zheng J, Williams CC, Lang A, et al. (2012) The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis. eLIFE 1: e00048. doi: 10.7554/eLife.00048 23066505

35. Deng Y, Srivastava R, Howell SH (2013) Protein kinase and ribonuclease domains of IRE1 confer stress tolerance, vegetative growth, and reproductive development in Arabidopsis. Proc Natl Acad Sci USA 110: 19633–19638. doi: 10.1073/pnas.1314749110 24145452

36. Fujita M, Mizukado S, Fujita Y, Ichikawa T, Nakazawa M, et al. (2007) Identification of stress-tolerance-related transcription-factor genes via mini-scale Full-length cDNA Over-eXpressor (FOX) gene hunting system. Biochem Bioph Res Co 364: 250–257.

37. Liu JX, Srivastava R, Che P, Howell SH (2007) An endoplasmic reticulum stress response in Arabidopsis Is mediated by proteolytic processing and nuclear relocation of a membrane-associated transcription factor, bZIP28. Plant Cell 19: 4111–4119. 18156219

38. Ye CM, Chen S, Payton M, Dickman MB, Verchot J (2013) TGBp3 triggers the unfolded protein response and SKP1-dependent programmed cell death. Mol Plant Pathol 14: 241–255. doi: 10.1111/mpp.12000 23458484

39. Ye C, Dickman MB, Whitham SA, Payton M, Verchot J (2011) The unfolded protein response is triggered by a plant viral movement protein. Plant Physiol 156: 741–755. doi: 10.1104/pp.111.174110 21474436

40. Wei T, Zhang C, Hong J, Xiong R, Kasschau KD, et al. (2010) Formation of complexes at plasmodesmata for potyvirus intercellular movement is mediated by the viral protein P3N-PIPO. PLoS Pathog 6: e1000962.

41. Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31: 3406–3415. 12824337

42. Lu DP, Christopher DA (2008) Endoplasmic reticulum stress activates the expression of a sub-group of protein disulfide isomerase genes and AtbZIP60 modulates the response in Arabidopsis thaliana. Mol Genet Genomics 280: 199–210. doi: 10.1007/s00438-008-0356-z 18574595

43. Francis KE, Lam SY, Copenhaver GP (2006) Separation of Arabidopsis pollen tetrads is regulated by QUARTET1, a pectin methylesterase gene. Plant Physiol 142: 1004–1013. 16980565

44. Brameier M, Krings A, MacCallum RM (2007) NucPred—predicting nuclear localization of proteins. Bioinformatics 23: 1159–1160. 17332022

45. Fontes MR, Teh T, Kobe B (2000) Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-α. J Mol Biol 297: 1183–1194. 10764582

46. Vinson C, Myakishev M, Acharya A, Mir AA, Moll JR, et al. (2002) Classification of human B-ZIP proteins based on dimerization properties. Mol Cell Biol 22: 6321–6335. 12192032

47. Pincus D, Chevalier MW, Aragón T, Van Anken E, Vidal SE, et al. (2010) BiP binding to the ER-stress sensor Ire1 tunes the homeostatic behavior of the unfolded protein response. PLoS Biol 8: e1000415. doi: 10.1371/journal.pbio.1000415 20625545

48. Pal B, Chan NC, Helfenbaum L, Tan K, Tansey WP, et al. (2007) SCFCdc4-mediated degradation of the Hac1p transcription factor regulates the unfolded protein response in Saccharomyces cerevisiae. Mol Biol Cell 18: 426–440. 17108329

49. Iwata Y, Yoneda M, Yanagawa Y, Koizumi N (2009) Characteristics of the nuclear form of the Arabidopsis transcription factor AtbZIP60 during the endoplasmic reticulum stress response. Biosci Biotech Bioch 73: 865–869.

50. Valkonen M, Penttilä M, Saloheimo M (2003) Effects of inactivation and constitutive expression of the unfolded-protein response pathway on protein production in the yeast Saccharomyces cerevisiae. Appl Environ Microbiol 69: 2065–2072. 12676684

51. Humbert S, Zhong S, Deng Y, Howell SH, Rothstein SJ (2012) Alteration of the bZIP60/IRE1 pathway affects plant response to ER stress in Arabidopsis thaliana. PloS one 7: e39023. doi: 10.1371/journal.pone.0039023 22701744

52. Iwata Y, Fedoroff NV, Koizumi N (2008) Arabidopsis bZIP60 is a proteolysis-activated transcription factor involved in the endoplasmic reticulum stress response. Plant Cell 20: 3107–3121. doi: 10.1105/tpc.108.061002 19017746

53. Tajima H, Iwata Y, Iwano M, Takayama S, Koizumi N (2008) Identification of an Arabidopsis transmembrane bZIP transcription factor involved in the endoplasmic reticulum stress response. Biochem Biophys Res Commun 374: 242–247. doi: 10.1016/j.bbrc.2008.07.021 18634751

54. Jakoby M, Weisshaar B, Dröge-Laser W, Vicente-Carbajosa J, Tiedemann J, et al. (2002) bZIP transcription factors in Arabidopsis. Trends Plant Sci 7: 106–111. 11906833

55. Netherton CL, Parsley JC, Wileman T (2004) African swine fever virus inhibits induction of the stress-induced proapoptotic transcription factor CHOP/GADD153. J Virol 78: 10825–10828. 15367650

56. Tardif KD, Waris G, Siddiqui A (2005) Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol 13: 159–163. 15817385

57. Tardif KD, Mori K, Kaufman RJ, Siddiqui A (2004) Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response. J Biol Chem 279: 17158–17164. 14960590

58. Bechill J, Chen Z, Brewer JW, Baker SC (2008) Coronavirus infection modulates the unfolded protein response and mediates sustained translational repression. J Virol 82: 4492–4501. doi: 10.1128/JVI.00017-08 18305036

59. Medigeshi GR, Lancaster AM, Hirsch AJ, Briese T, Lipkin WI, et al. (2007) West Nile virus infection activates the unfolded protein response, leading to CHOP induction and apoptosis. J Virol 81: 10849–10860. 17686866

60. DeSalvo J, Kuznetsov JN, Du J, Leclerc GM, Leclerc GJ, et al. (2012) Inhibition of Akt potentiates 2-DG–Induced apoptosis via downregulation of UPR in acute lymphoblastic leukemia. Mol Cancer Res 10: 969–978. doi: 10.1158/1541-7786.MCR-12-0125 22692960

61. Adolph TE, Tomczak MF, Niederreiter L, Ko H-J, Böck J, et al. (2013) Paneth cells as a site of origin for intestinal inflammation. Nature 503: 272–276. doi: 10.1038/nature12599 24089213

62. Hassan IH, Zhang MS, Powers LS, Shao JQ, Baltrusaitis J, et al. (2012) Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. J Biol Chem 287: 4679–4689. doi: 10.1074/jbc.M111.284695 22194594

63. Yang C, Guo R, Jie F, Nettleton D, Peng J, et al. (2007) Spatial analysis of Arabidopsis thaliana gene expression in response to Turnip mosaic virus infection. Mol Plant Microbe Interact 20: 358–370. 17427806

64. García-Marcos A, Pacheco R, Martiáñez J, González-Jara P, Díaz-Ruíz JR, et al. (2009) Transcriptional changes and oxidative stress associated with the synergistic interaction between Potato virus X and Potato virus Y and their relationship with symptom expression. Mol Plant Microbe Interact 22: 1431–1444. doi: 10.1094/MPMI-22-11-1431 19810812

65. Whitham SA, Quan S, Chang HS, Cooper B, Estes B, et al. (2003) Diverse RNA viruses elicit the expression of common sets of genes in susceptible Arabidopsis thaliana plants. Plant J 33: 271–283.

66. Hafrén A, Hofius D, Rönnholm G, Sonnewald U, Mäkinen K (2010) HSP70 and its cochaperone CPIP promote potyvirus infection in Nicotiana benthamiana by regulating viral coat protein functions. Plant Cell 22: 523–535. doi: 10.1105/tpc.109.072413 20154150

67. Pogany J, Stork J, Li Z, Nagy PD (2008) In vitro assembly of the Tomato bushy stunt virus replicase requires the host Heat shock protein 70. Proc Natl Acad Sci USA 105: 19956–19961. doi: 10.1073/pnas.0810851105 19060219

68. Serva S, Nagy PD (2006) Proteomics analysis of the tombusvirus replicase: Hsp70 molecular chaperone is associated with the replicase and enhances viral RNA replication. J Virol 80: 2162–2169. 16474124

69. Sugio A, Dreos R, Aparicio F, Maule AJ (2009) The cytosolic protein response as a subcomponent of the wider heat shock response in Arabidopsis. Plant Cell 21: 642–654.

70. Aparicio F, Thomas CL, Lederer C, Niu Y, Wang D, et al. (2005) Virus induction of heat shock protein 70 reflects a general response to protein accumulation in the plant cytosol. Plant Physiol 138: 529–536. 15805473

71. Jungkunz I, Link K, Vogel F, Voll LM, Sonnewald S, et al. (2011) AtHsp70-15-deficient Arabidopsis plants are characterized by reduced growth, a constitutive cytosolic protein response and enhanced resistance to TuMV. Plant J 66: 983–995. doi: 10.1111/j.1365-313X.2011.04558.x 21418353

72. Maruyama D, Endo T, Nishikawa S-i (2010) BiP-mediated polar nuclei fusion is essential for the regulation of endosperm nuclei proliferation in Arabidopsis thaliana. Proc Natl Acad Sci USA 107: 1684–1689. doi: 10.1073/pnas.0905795107 20080634

73. Watowich SS, Morimoto RI, Lamb RA (1991) Flux of the paramyxovirus hemagglutinin-neuraminidase glycoprotein through the endoplasmic reticulum activates transcription of the GRP78-BiP gene. J Virol 65: 3590–3597. 2041085

74. Sung SC, Chao CY, Jeng KS, Yang JY, Lai M (2009) The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6. Virology 387: 402–413. doi: 10.1016/j.virol.2009.02.021 19304306

75. Bamunusinghe D, Hemenway CL, Nelson RS, Sanderfoot AA, Ye CM, et al. (2009) Analysis of potato virus X replicase and TGBp3 subcellular locations. Virology 393: 272–285. doi: 10.1016/j.virol.2009.08.002 19729179

76. Niwa M, Patil CK, DeRisi J, Walter P (2005) Genome-scale approaches for discovering novel nonconventional splicing substrates of the Ire1 nuclease. Genome Biol 6: R3.

77. Shen X, Ellis RE, Sakaki K, Kaufman RJ (2005) Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genet 1: e37. 16184190

78. Urano F, Wang XZ, Bertolotti A, Zhang Y, Chung P, et al. (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287: 664–666. 10650002

79. Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, et al. (2006) Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1α. Science 312: 572–576. 16645094

80. Upton J-P, Wang L, Han D, Wang ES, Huskey NE, et al. (2012) IRE1α cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science 338: 818–822. doi: 10.1126/science.1226191 23042294

81. Cross BC, Ron D (2012) New twists in the unfolded protein response. eLIFE 1: e00243. doi: 10.7554/eLife.00243 23066509

82. Huang TS, Wei T, Laliberte JF, Wang A (2010) A host RNA helicase-like protein, AtRH8, interacts with the potyviral genome-linked protein, VPg, associates with the virus accumulation complex, and is essential for infection. Plant Physiol 152: 255–266. doi: 10.1104/pp.109.147983 19880609

83. Clough SJ, Bent AF (1998) Floral dip: a simplified method forAgrobacterium-mediated transformation ofArabidopsis thaliana. Plant J 16: 735–743. 10069079

84. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ (2009) Jalview Version 2-a multiple sequence alignment editor and analysis workbench. Bioinformatics 25: 1189–1191. doi: 10.1093/bioinformatics/btp033 19151095