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A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases


During replication of Kaposi’s sarcoma-associated herpesvirus (KSHV), the vast majority of mRNAs in the cytoplasm are cleaved and degraded by the viral nuclease SOX. However, some mRNAs escape this fate, including the transcript encoding the immunoregulatory cytokine IL-6. Here, we discover that this escape is mediated by a group of proteins that associates with a sequence element on the IL-6 mRNA. One of these proteins is nucleolin (NCL), a factor with diverse roles in RNA processing that is frequently co-opted during viral infection. During KSHV replication, a proportion of NCL is redirected from the nucleolar subcompartment of the nucleus into the cytoplasm, where it binds both the IL-6 3’ UTR and a complex of cellular proteins including the translation initiation factor eIF4H. This network of interactions is required for escape from virus-induced degradation. Collectively, these findings reveal novel interplay between the SOX escapees and the cellular mRNA stabilization machinery, and shed light on the complex crosstalk between viruses and hosts over the control of gene expression.


Vyšlo v časopise: A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004899
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004899

Souhrn

During replication of Kaposi’s sarcoma-associated herpesvirus (KSHV), the vast majority of mRNAs in the cytoplasm are cleaved and degraded by the viral nuclease SOX. However, some mRNAs escape this fate, including the transcript encoding the immunoregulatory cytokine IL-6. Here, we discover that this escape is mediated by a group of proteins that associates with a sequence element on the IL-6 mRNA. One of these proteins is nucleolin (NCL), a factor with diverse roles in RNA processing that is frequently co-opted during viral infection. During KSHV replication, a proportion of NCL is redirected from the nucleolar subcompartment of the nucleus into the cytoplasm, where it binds both the IL-6 3’ UTR and a complex of cellular proteins including the translation initiation factor eIF4H. This network of interactions is required for escape from virus-induced degradation. Collectively, these findings reveal novel interplay between the SOX escapees and the cellular mRNA stabilization machinery, and shed light on the complex crosstalk between viruses and hosts over the control of gene expression.


Zdroje

1. Moore MJ. From birth to death: the complex lives of eukaryotic mRNAs. Science. 2005; 309: 1514–1518. 16141059

2. Chen CY, Shyu AB. Mechanisms of deadenylation-dependent decay. Wiley Interdiscip Rev RNA. 2011; 2: 167–183. doi: 10.1002/wrna.40 21957004

3. Shim J, Karin M. The control of mRNA stability in response to extracellular stimuli. Mol Cells. 2002; 14: 323–331. 12521293

4. Thapar R, Denmon AP. Signaling pathways that control mRNA turnover. Cell Signal. 2013; 25: 1699–1710. doi: 10.1016/j.cellsig.2013.03.026 23602935

5. Clyde K, Glaunsinger BA. Getting the message direct manipulation of host mRNA accumulation during gammaherpesvirus lytic infection. Adv Virus Res. 2010; 78: 1–42. doi: 10.1016/B978-0-12-385032-4.00001-X 21040830

6. Moon SL, Wilusz J. Cytoplasmic viruses: rage against the (cellular RNA decay) machine. PLoS Pathog. 2013; 9: e1003762. doi: 10.1371/journal.ppat.1003762 24339774

7. Abernathy E, Clyde K, Yeasmin R, Krug LT, Burlingame A, et al. Gammaherpesviral gene expression and virion composition are broadly controlled by accelerated mRNA degradation. PLoS Pathog. 2014; 10: e1003882. doi: 10.1371/journal.ppat.1003882 24453974

8. Glaunsinger B, Ganem D. Lytic KSHV infection inhibits host gene expression by accelerating global mRNA turnover. Mol Cell. 2004; 13: 713–723. 15023341

9. Richner JM, Clyde K, Pezda AC, Cheng BY, Wang T, et al. Global mRNA degradation during lytic gammaherpesvirus infection contributes to establishment of viral latency. PLoS Pathog. 2011; 7: e1002150. doi: 10.1371/journal.ppat.1002150 21811408

10. Rowe M, Glaunsinger B, van Leeuwen D, Zuo J, Sweetman D, et al. Host shutoff during productive Epstein-Barr virus infection is mediated by BGLF5 and may contribute to immune evasion. Proc Natl Acad Sci U S A. 2007; 104: 3366–3371. 17360652

11. Covarrubias S, Gaglia MM, Kumar GR, Wong W, Jackson AO, et al. Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1. PLoS Pathog. 2011; 7: e1002339. doi: 10.1371/journal.ppat.1002339 22046136

12. Chandriani S, Ganem D. Host transcript accumulation during lytic KSHV infection reveals several classes of host responses. PLoS One. 2007; 2: e811. 17726541

13. Clyde K, Glaunsinger BA. Deep sequencing reveals direct targets of gammaherpesvirus-induced mRNA decay and suggests that multiple mechanisms govern cellular transcript escape. PLoS One. 2011; 6: e19655. doi: 10.1371/journal.pone.0019655 21573023

14. Asou H, Said JW, Yang R, Munker R, Park DJ, et al. Mechanisms of growth control of Kaposi's sarcoma-associated herpes virus-associated primary effusion lymphoma cells. Blood. 1998; 91: 2475–2481. 9516148

15. Leger-Ravet MB, Peuchmaur M, Devergne O, Audouin J, Raphael M, et al. Interleukin-6 gene expression in Castleman's disease. Blood. 1991; 78: 2923–2930. 1954381

16. Screpanti I, Musiani P, Bellavia D, Cappelletti M, Aiello FB, et al. Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice. J Exp Med. 1996; 184: 1561–1566. 8879230

17. Glaunsinger B, Ganem D. Highly selective escape from KSHV-mediated host mRNA shutoff and its implications for viral pathogenesis. J Exp Med. 2004; 200: 391–398. 15289507

18. Hutin S, Lee Y, Glaunsinger BA. An RNA element in human interleukin 6 confers escape from degradation by the gammaherpesvirus SOX protein. J Virol. 2013; 87: 4672–4682. doi: 10.1128/JVI.00159-13 23408619

19. Lee HY, Haurwitz RE, Apffel A, Zhou K, Smart B, et al. RNA-protein analysis using a conditional CRISPR nuclease. Proc Natl Acad Sci U S A. 2013; 110: 5416–5421. doi: 10.1073/pnas.1302807110 23493562

20. Abdelmohsen K, Gorospe M. RNA-binding protein nucleolin in disease. RNA Biol. 2012; 9: 799–808. doi: 10.4161/rna.19718 22617883

21. Serin G, Joseph G, Ghisolfi L, Bauzan M, Erard M, et al. Two RNA-binding domains determine the RNA-binding specificity of nucleolin. J Biol Chem. 1997; 272: 13109–13116. 9148924

22. Borer RA, Lehner CF, Eppenberger HM, Nigg EA. Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell. 1989; 56: 379–390. 2914325

23. Ginisty H, Sicard H, Roger B, Bouvet P. Structure and functions of nucleolin. J Cell Sci. 1999; 112 (Pt 6): 761–772.

24. Covarrubias S, Richner JM, Clyde K, Lee YJ, Glaunsinger BA. Host shutoff is a conserved phenotype of gammaherpesvirus infection and is orchestrated exclusively from the cytoplasm. J Virol. 2009; 83: 9554–9566. doi: 10.1128/JVI.01051-09 19587049

25. Glaunsinger B, Chavez L, Ganem D. The exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable. J Virol. 2005; 79: 7396–7401. 15919895

26. Tuteja R, Tuteja N. Nucleolin: a multifunctional major nucleolar phosphoprotein. Crit Rev Biochem Mol Biol. 1998; 33: 407–436. 9918513

27. Myoung J, Ganem D. Infection of lymphoblastoid cell lines by Kaposi's sarcoma-associated herpesvirus: critical role of cell-associated virus. J Virol. 2011; 85: 9767–9777. doi: 10.1128/JVI.05136-11 21795352

28. Creancier L, Prats H, Zanibellato C, Amalric F, Bugler B. Determination of the functional domains involved in nucleolar targeting of nucleolin. Mol Biol Cell. 1993; 4: 1239–1250. 8167407

29. Deng H, Chu JT, Rettig MB, Martinez-Maza O, Sun R. Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression. Blood. 2002; 100: 1919–1921. 12176919

30. McCormick C, Ganem D. The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs. Science. 2005; 307: 739–741. 15692053

31. Bouvet P, Diaz JJ, Kindbeiter K, Madjar JJ, Amalric F. Nucleolin interacts with several ribosomal proteins through its RGG domain. J Biol Chem. 1998; 273: 19025–19029. 9668083

32. Goldstein M, Derheimer FA, Tait-Mulder J, Kastan MB. Nucleolin mediates nucleosome disruption critical for DNA double-strand break repair. Proc Natl Acad Sci U S A. 2013; 110: 16874–16879. doi: 10.1073/pnas.1306160110 24082117

33. Kusakawa T, Shimakami T, Kaneko S, Yoshioka K, Murakami S. Functional interaction of hepatitis C Virus NS5B with Nucleolin GAR domain. J Biochem. 2007; 141: 917–927. 17569707

34. Taha MS, Nouri K, Milroy LG, Moll JM, Herrmann C, et al. Subcellular fractionation and localization studies reveal a direct interaction of the fragile X mental retardation protein (FMRP) with nucleolin. PLoS One. 2014; 9: e91465. doi: 10.1371/journal.pone.0091465 24658146

35. Thandapani P, O'Connor TR, Bailey TL, Richard S. Defining the RGG/RG motif. Mol Cell. 2013; 50: 613–623. doi: 10.1016/j.molcel.2013.05.021 23746349

36. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012; 485: 55–61. doi: 10.1038/nature10912 22367541

37. Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, et al. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature. 2012; 485: 109–113. doi: 10.1038/nature11083 22552098

38. Gaglia MM, Glaunsinger BA. Viruses and the cellular RNA decay machinery. Wiley Interdiscip Rev RNA. 2010; 1: 47–59. doi: 10.1002/wrna.3 21956906

39. Narayanan K, Makino S. Interplay between viruses and host mRNA degradation. Biochim Biophys Acta. 2013; 1829: 732–741. doi: 10.1016/j.bbagrm.2012.12.003 23274304

40. Read GS. Virus-encoded endonucleases: expected and novel functions. Wiley Interdiscip Rev RNA. 2013; 4: 693–708. doi: 10.1002/wrna.1188 23900973

41. Elgadi MM, Hayes CE, Smiley JR. The herpes simplex virus vhs protein induces endoribonucleolytic cleavage of target RNAs in cell extracts. J Virol. 1999; 73: 7153–7164. 10438802

42. Kwong AD, Frenkel N. The herpes simplex virus virion host shutoff function. J Virol. 1989; 63: 4834–4839. 2552156

43. Sorenson CM, Hart PA, Ross J. Analysis of herpes simplex virus-induced mRNA destabilizing activity using an in vitro mRNA decay system. Nucleic Acids Res. 1991; 19: 4459–4465. 1653415

44. Zelus BD, Stewart RS, Ross J. The virion host shutoff protein of herpes simplex virus type 1: messenger ribonucleolytic activity in vitro. J Virol. 1996; 70: 2411–2419. 8642669

45. Smiley JR, Elgadi MM, Saffran HA. Herpes simplex virus vhs protein. Methods Enzymol. 2001; 342: 440–451. 11586916

46. Gaglia MM, Covarrubias S, Wong W, Glaunsinger BA. A common strategy for host RNA degradation by divergent viruses. J Virol. 2012; 86: 9527–9530. doi: 10.1128/JVI.01230-12 22740404

47. Krikorian CR, Read GS. In vitro mRNA degradation system to study the virion host shutoff function of herpes simplex virus. J Virol. 1991; 65: 112–122. 1845879

48. Shiflett LA, Read GS. mRNA decay during herpes simplex virus (HSV) infections: mutations that affect translation of an mRNA influence the sites at which it is cleaved by the HSV virion host shutoff (Vhs) protein. J Virol. 2013; 87: 94–109. doi: 10.1128/JVI.01557-12 23077305

49. Feng P, Everly DN Jr., Read GS. mRNA decay during herpes simplex virus (HSV) infections: protein-protein interactions involving the HSV virion host shutoff protein and translation factors eIF4H and eIF4A. J Virol. 2005; 79: 9651–9664. 16014927

50. Page HG, Read GS. The virion host shutoff endonuclease (UL41) of herpes simplex virus interacts with the cellular cap-binding complex eIF4F. J Virol. 2010; 84: 6886–6890. doi: 10.1128/JVI.00166-10 20427534

51. Karr BM, Read GS. The virion host shutoff function of herpes simplex virus degrades the 5' end of a target mRNA before the 3' end. Virology. 1999; 264: 195–204. 10544145

52. Feng P, Everly DN Jr., Read GS. mRNA decay during herpesvirus infections: interaction between a putative viral nuclease and a cellular translation factor. J Virol. 2001; 75: 10272–10280. 11581395

53. Sarma N, Agarwal D, Shiflett LA, Read GS. Small interfering RNAs that deplete the cellular translation factor eIF4H impede mRNA degradation by the virion host shutoff protein of herpes simplex virus. J Virol. 2008; 82: 6600–6609. doi: 10.1128/JVI.00137-08 18448541

54. Esclatine A, Taddeo B, Evans L, Roizman B. The herpes simplex virus 1 UL41 gene-dependent destabilization of cellular RNAs is selective and may be sequence-specific. Proc Natl Acad Sci U S A. 2004; 101: 3603–3608. 14993598

55. Esclatine A, Taddeo B, Roizman B. The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs. Proc Natl Acad Sci U S A. 2004; 101: 18165–18170. 15596716

56. Corcoran JA, Hsu WL, Smiley JR. Herpes simplex virus ICP27 is required for virus-induced stabilization of the ARE-containing IEX-1 mRNA encoded by the human IER3 gene. J Virol. 2006; 80: 9720–9729. 16973576

57. Esclatine A, Taddeo B, Roizman B. Herpes simplex virus 1 induces cytoplasmic accumulation of TIA-1/TIAR and both synthesis and cytoplasmic accumulation of tristetraprolin, two cellular proteins that bind and destabilize AU-rich RNAs. J Virol. 2004; 78: 8582–8592. 15280467

58. Hsu WL, Saffran HA, Smiley JR. Herpes simplex virus infection stabilizes cellular IEX-1 mRNA. J Virol. 2005; 79: 4090–4098. 15767410

59. Taddeo B, Zhang W, Roizman B. Role of herpes simplex virus ICP27 in the degradation of mRNA by virion host shutoff RNase. J Virol. 2010; 84: 10182–10190. doi: 10.1128/JVI.00975-10 20631134

60. Chen CY, Gherzi R, Andersen JS, Gaietta G, Jurchott K, et al. Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes Dev. 2000; 14: 1236–1248. 10817758

61. Jiang Y, Xu XS, Russell JE. A nucleolin-binding 3' untranslated region element stabilizes beta-globin mRNA in vivo. Mol Cell Biol. 2006; 26: 2419–2429. 16508016

62. Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, et al. Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA. Blood. 2007; 109: 3069–3075. 17179226

63. Zhang Y, Bhatia D, Xia H, Castranova V, Shi X, et al. Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA. Nucleic Acids Res. 2006; 34: 485–495. 16421274

64. Zaidi SH, Malter JS. Nucleolin and heterogeneous nuclear ribonucleoprotein C proteins specifically interact with the 3'-untranslated region of amyloid protein precursor mRNA. J Biol Chem. 1995; 270: 17292–17298. 7615529

65. Sengupta TK, Bandyopadhyay S, Fernandes DJ, Spicer EK. Identification of nucleolin as an AU-rich element binding protein involved in bcl-2 mRNA stabilization. J Biol Chem. 2004; 279: 10855–10863. 14679209

66. Taddeo B, Esclatine A, Roizman B. The patterns of accumulation of cellular RNAs in cells infected with a wild-type and a mutant herpes simplex virus 1 lacking the virion host shutoff gene. Proc Natl Acad Sci U S A. 2002; 99: 17031–17036. 12481033

67. Barreau C, Paillard L, Osborne HB. AU-rich elements and associated factors: are there unifying principles? Nucleic Acids Res. 2005; 33: 7138–7150. 16391004

68. Ishimaru D, Zuraw L, Ramalingam S, Sengupta TK, Bandyopadhyay S, et al. Mechanism of regulation of bcl-2 mRNA by nucleolin and A+U-rich element-binding factor 1 (AUF1). J Biol Chem. 2010; 285: 27182–27191. doi: 10.1074/jbc.M109.098830 20571027

69. Li YP, Busch RK, Valdez BC, Busch H. C23 interacts with B23, a putative nucleolar-localization-signal-binding protein. Eur J Biochem. 1996; 237: 153–158. 8620867

70. Yu Y, Maggi LB Jr., Brady SN, Apicelli AJ, Dai MS, et al. Nucleophosmin is essential for ribosomal protein L5 nuclear export. Mol Cell Biol. 2006; 26: 3798–3809. 16648475

71. Brendel C, Rehbein M, Kreienkamp HJ, Buck F, Richter D, et al. Characterization of Staufen 1 ribonucleoprotein complexes. Biochem J. 2004; 384: 239–246. 15303970

72. Villace P, Marion RM, Ortin J. The composition of Staufen-containing RNA granules from human cells indicates their role in the regulated transport and translation of messenger RNAs. Nucleic Acids Res. 2004; 32: 2411–2420. 15121898

73. Parsyan A, Svitkin Y, Shahbazian D, Gkogkas C, Lasko P, et al. mRNA helicases: the tacticians of translational control. Nat Rev Mol Cell Biol. 2011; 12: 235–245. doi: 10.1038/nrm3083 21427765

74. Rogers GW Jr., Richter NJ, Lima WF, Merrick WC. Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F. J Biol Chem. 2001; 276: 30914–30922. 11418588

75. Calle A, Ugrinova I, Epstein AL, Bouvet P, Diaz JJ, et al. Nucleolin is required for an efficient herpes simplex virus type 1 infection. J Virol. 2008; 82: 4762–4773. doi: 10.1128/JVI.00077-08 18321972

76. Gao W, Li M, Zhang J. Tandem immunoprecipitation approach to identify HIV-1 Gag associated host factors. J Virol Methods. 2014; 203: 116–119. doi: 10.1016/j.jviromet.2014.03.017 24690621

77. Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, et al. Identification of nucleolin as a cellular receptor for human respiratory syncytial virus. Nat Med. 2011; 17: 1132–1135. doi: 10.1038/nm.2444 21841784

78. Waggoner S, Sarnow P. Viral ribonucleoprotein complex formation and nucleolar-cytoplasmic relocalization of nucleolin in poliovirus-infected cells. J Virol. 1998; 72: 6699–6709. 9658117

79. Bertrand L, Leiva-Torres GA, Hyjazie H, Pearson A. Conserved residues in the UL24 protein of herpes simplex virus 1 are important for dispersal of the nucleolar protein nucleolin. J Virol. 2010; 84: 109–118. doi: 10.1128/JVI.01428-09 19864385

80. Lymberopoulos MH, Pearson A. Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin. Virology. 2007; 363: 397–409. 17346762

81. Wang WH, Childress MO, Geahlen RL. Syk interacts with and phosphorylates nucleolin to stabilize Bcl-x(L) mRNA and promote cell survival. Mol Cell Biol. 2014; 34: 3788–3799. doi: 10.1128/MCB.00937-14 25092868

82. Wu DM, Zhang P, Liu RY, Sang YX, Zhou C, et al. Phosphorylation and changes in the distribution of nucleolin promote tumor metastasis via the PI3K/Akt pathway in colorectal carcinoma. FEBS Lett. 2014; 588: 1921–1929. doi: 10.1016/j.febslet.2014.03.047 24713430

83. Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner SL, et al. Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol. 2003; 77: 4205–4220. 12634378

84. Myoung J, Ganem D. Generation of a doxycycline-inducible KSHV producer cell line of endothelial origin: maintenance of tight latency with efficient reactivation upon induction. J Virol Methods. 2011; 174: 12–21. doi: 10.1016/j.jviromet.2011.03.012 21419799

85. Haurwitz RE, Jinek M, Wiedenheft B, Zhou K, Doudna JA. Sequence- and structure-specific RNA processing by a CRISPR endonuclease. Science. 2010; 329: 1355–1358. doi: 10.1126/science.1192272 20829488

86. Guan S, Price JC, Prusiner SB, Ghaemmaghami S, Burlingame AL. A data processing pipeline for mammalian proteome dynamics studies using stable isotope metabolic labeling. Mol Cell Proteomics. 2011; 10: M111 010728.

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