リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Defining the molecular role of RNA helicase DDX3 in antiviral signaling pathways」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Defining the molecular role of RNA helicase DDX3 in antiviral signaling pathways

SAIKRUANG, WILAIPORN 京都大学 DOI:10.14989/doctor.k24119

2022.05.23

概要

The human DEAD-box protein 3 (DDX3) is an ATP-dependent RNA helicase that has been shown to have a range of cellular processes, including transcription, translation, and mRNA export. DDX3 has also been shown to play a dual function in viral replication: as a cofactor of virus replication and as a mediator of the innate immunity system. There have been several studies on the regulation of innate antiviral immunity by DDX3; however, the biological function of DDX3 in innate antiviral immunity is still not fully understood.

My doctoral research study aimed to elucidate the function of DDX3 on the molecular level and understand its role in the positive regulation of IFN-β production. Experiments presented here revealed that DDX3 mediates virus-induced activation of IFNB at the level of IRF-3. However, DDX3 does not affect conventional innate signaling, including IRF-3 phosphorylation, dimerization, and nuclear translocation of IRF-3 but has some downstream events after IRF-3 phosphorylation. DDX3 interacts with IRF-3 through its DNA-binding domain and promotes IRF- 3-mediated IFNB promoter activation. DDX3 interacts with IRF-3 through its DNA-binding domain and increases IRF-3-mediated IFNB promoter activation, according to coimmunoprecipitation analysis. Additionally, the formation of the IRF-3/p300/CBP complex is unaffected by DDX3. Instead, DDX3 promotes recruitment of IRF-3 and transcriptional co- activator p300/CBP to the IFNB promoter and facilitates the transcription of IFNB. Furthermore, DDX3’s ATP binding pocket is involved in the association between DDX3 and IRF-3 and critical for IFNB transcriptional activation. Taken together, this study revealed a novel function of that DDX3 in guiding a transcription factor complex formed by antiviral signaling to IFNB promoter in response to viral infection.

この論文で使われている画像

参考文献

1. Akira S, Uematsu S, Takeuchi O. Pathogen Recognition and Innate Immunity. Cell. 2006 Feb;124(4):783–801.

2. Kell AM, Gale M. RIG-I in RNA virus recognition. Virology. 2015 May;479–480:110– 21.

3. Hartmann G. Nucleic Acid Immunity. In 2017. p. 121–69.

4. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology. 2010 May 20;11(5):373–84.

5. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, et al. Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity. The Journal of Immunology. 2005 Sep 1;175(5):2851–8.

6. Rodriguez KR, Bruns AM, Horvath CM. MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal Transduction. Journal of Virology. 2014 Aug 1;88(15):8194–200.

7. Schmidt A, Schwerd T, Hamm W, Hellmuth JC, Cui S, Wenzel M, et al. 5’-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I. Proceedings of the National Academy of Sciences. 2009 Jul 21;106(29):12067–72.

8. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006 May 9;441(7089):101–5.

9. Saito T, Gale M. Differential recognition of double-stranded RNA by RIG-I–like receptors in antiviral immunity. Journal of Experimental Medicine. 2008 Jul 7;205(7):1523–7.

10. Berke IC, Modis Y. MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA. The EMBO Journal. 2012 Apr 4;31(7):1714–26.

11. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006 May 9;441(7089):101–5.

12. Brisse M, Ly H. Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5. Frontiers in Immunology. 2019 Jul 17;10.

13. Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, Kato H, et al. 5’-Triphosphate RNA Is the Ligand for RIG-I. Science (1979). 2006 Nov 10;314(5801):994–7.

14. Xu L-G, Wang Y-Y, Han K-J, Li L-Y, Zhai Z, Shu H-B. VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling. Molecular Cell. 2005 Sep;19(6):727–40.

15. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nature Immunology. 2005 Oct 28;6(10):981–8.

16. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005 Oct 21;437(7062):1167–72.

17. Rehwinkel J, Gack MU. RIG-I-like receptors: their regulation and roles in RNA sensing. Nature Reviews Immunology. 2020 Sep 13;20(9):537–51.

18. Darnell J, Kerr I, Stark G. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science (1979). 1994 Jun 3;264(5164).

19. Schindler C, Levy DE, Decker T. JAK-STAT Signaling: From Interferons to Cytokines. Journal of Biological Chemistry. 2007 Jul;282(28):20059–63.

20. Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nature Reviews Immunology. 2006 Sep;6(9):644– 58.

21. Lin R, Heylbroeck C, Pitha PM, Hiscott J. Virus-Dependent Phosphorylation of the IRF-3 Transcription Factor Regulates Nuclear Translocation, Transactivation Potential, and Proteasome-Mediated Degradation. Molecular and Cellular Biology. 1998 May;18(5):2986–96.

22. Sharma S, tenOever BR, Grandvaux N, Zhou G-P, Lin R, Hiscott J. Triggering the Interferon Antiviral Response Through an IKK-Related Pathway. Science (1979). 2003 May 16;300(5622):1148–51.

23. Servant MJ, Grandvaux N, tenOever BR, Duguay D, Lin R, Hiscott J. Identification of the Minimal Phosphoacceptor Site Required for in Vivo Activation of Interferon Regulatory Factor 3 in Response to Virus and Double-stranded RNA. Journal of Biological Chemistry. 2003 Mar;278(11):9441–7.

24. Mori M, Yoneyama M, Ito T, Takahashi K, Inagaki F, Fujita T. Identification of Ser-386 of Interferon Regulatory Factor 3 as Critical Target for Inducible Phosphorylation That Determines Activation. Journal of Biological Chemistry. 2004 Mar;279(11):9698–702.

25. Suhara W, Yoneyama M, Kitabayashi I, Fujita T. Direct Involvement of CREB-binding Protein/p300 in Sequence-specific DNA Binding of Virus-activated Interferon Regulatory Factor-3 Holocomplex. Journal of Biological Chemistry. 2002 Jun;277(25).

26. Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nature Reviews Immunology. 2006 Sep;6(9):644– 58.

27. Jankowsky E. RNA helicases at work: binding and rearranging. Trends in Biochemical Sciences. 2011 Jan;36(1).

28. Cordin O, Banroques J, Tanner NK, Linder P. The DEAD-box protein family of RNA helicases. Gene. 2006 Feb;367.

29. LINDER P, LASKO PF, ASHBURNER M, LEROY P, NIELSEN PJ, NISHI K, et al. Birth of the D-E-A-D box. Nature. 1989 Jan;337(6203):121–2.

30. Park SH, Lee S-G, Kim Y, Song K. Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3-->p11.23. Cytogenetic and Genome Research. 1998;81(3–4).

31. Lahn BT. Functional Coherence of the Human Y Chromosome. Science (1979). 1997 Oct 24;278(5338).

32. Ditton HJ. The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Human Molecular Genetics. 2004 Aug 4;13(19).

33. Szappanos D, Tschismarov R, Perlot T, Westermayer S, Fischer K, Platanitis E, et al. The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity. PLOS Pathogens. 2018 Nov 26;14(11):e1007397.

34. Hernández-Díaz T, Valiente-Echeverría F, Soto-Rifo R. RNA Helicase DDX3: A Double- Edged Sword for Viral Replication and Immune Signaling. Microorganisms. 2021 Jun 3;9(6):1206.

35. Fuller-Pace F v. DExD/H box RNA helicases: multifunctional proteins with important roles in transcriptional regulation. Nucleic Acids Research. 2006 Sep;34(15).

36. Linder P, Jankowsky E. From unwinding to clamping — the DEAD box RNA helicase family. Nature Reviews Molecular Cell Biology. 2011 Aug 22;12(8).

37. Ariumi Y. Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection. Frontiers in Genetics. 2014 Dec 5;5.

38. Epling LB, Grace CR, Lowe BR, Partridge JF, Enemark EJ. Cancer-Associated Mutants of RNA Helicase DDX3X Are Defective in RNA-Stimulated ATP Hydrolysis. Journal of Molecular Biology. 2015 May;427(9):1779–96.

39. Lai M-C, Chang W-C, Shieh S-Y, Tarn W-Y. DDX3 Regulates Cell Growth through Translational Control of Cyclin E1. Molecular and Cellular Biology. 2010 Nov 15;30(22):5444–53.

40. Upadya MH. Understanding the interaction of hepatitis C virus with host DEAD-box RNA helicases. World Journal of Gastroenterology. 2014;20(11):2913.

41. Kumar R, Singh N, Abdin MZ, Patel AH, Medigeshi GR. Dengue Virus Capsid Interacts with DDX3X–A Potential Mechanism for Suppression of Antiviral Functions in Dengue Infection. Frontiers in Cellular and Infection Microbiology. 2018 Jan 17;7.

42. Li G, Feng T, Pan W, Shi X, Dai J. DEAD-box RNA helicase DDX3X inhibits DENV replication via regulating type one interferon pathway. Biochemical and Biophysical Research Communications. 2015 Jan;456(1):327–32.

43. Li C, Ge L, Li P, Wang Y, Dai J, Sun M, et al. Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions. Virology. 2014 Jan;449:70–81.

44. Brai A, Martelli F, Riva V, Garbelli A, Fazi R, Zamperini C, et al. DDX3X Helicase Inhibitors as a New Strategy To Fight the West Nile Virus Infection. Journal of Medicinal Chemistry. 2019 Mar 14;62(5):2333–47.

45. Lorgeoux R-P, Guo F, Liang C. From promoting to inhibiting: diverse roles of helicases in HIV-1 Replication. Retrovirology. 2012 Dec 28;9(1):79.

46. Yedavalli VSRK, Neuveut C, Chi Y, Kleiman L, Jeang K-T. Requirement of DDX3 DEAD Box RNA Helicase for HIV-1 Rev-RRE Export Function. Cell. 2004 Oct;119(3):381–92.

47. Wang H, Kim S, Ryu W-S. DDX3 DEAD-Box RNA Helicase Inhibits Hepatitis B Virus Reverse Transcription by Incorporation into Nucleocapsids. Journal of Virology. 2009 Jun;83(11):5815–24.

48. Kalverda AP, Thompson GS, Vogel A, Schröder M, Bowie AG, Khan AR, et al. Poxvirus K7 Protein Adopts a Bcl-2 Fold: Biochemical Mapping of Its Interactions with Human DEAD Box RNA Helicase DDX3. Journal of Molecular Biology. 2009 Jan;385(3):843– 53.

49. Vashist S, Urena L, Chaudhry Y, Goodfellow I. Identification of RNA-Protein Interaction Networks Involved in the Norovirus Life Cycle. Journal of Virology. 2012 Nov 15;86(22):11977–90.

50. Thulasi Raman SN, Liu G, Pyo HM, Cui YC, Xu F, Ayalew LE, et al. DDX3 Interacts with Influenza A Virus NS1 and NP Proteins and Exerts Antiviral Function through Regulation of Stress Granule Formation. Journal of Virology. 2016 Apr;90(7):3661–75.

51. Soulat D, Bürckstümmer T, Westermayer S, Goncalves A, Bauch A, Stefanovic A, et al. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1- dependent innate immune response. The EMBO Journal. 2008 Aug 6;27(15).

52. Schröder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKɛ-mediated IRF activation. The EMBO Journal. 2008 Aug 6;27(15).

53. Chao C-H, Chen C-M, Cheng P-L, Shih J-W, Tsou A-P, Wu Lee Y-H. DDX3, a DEAD Box RNA Helicase with Tumor Growth–Suppressive Property and Transcriptional Regulation Activity of the p21 waf1/cip1 Promoter, Is a Candidate Tumor Suppressor. Cancer Research. 2006 Jul 1;66(13).

54. Botlagunta M, Vesuna F, Mironchik Y, Raman A, Lisok A, Winnard P, et al. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene. 2008 Jun 11;27(28):3912–22.

55. Sun M, Song L, Zhou T, Gillespie GY, Jope RS. The role of DDX3 in regulating Snail. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2011 Mar;1813(3):438–47.

56. Oshiumi H, Sakai K, Matsumoto M, Seya T. DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-β-inducing potential. European Journal of Immunology. 2010 Apr;40(4).

57. Oda S, Schröder M, Khan AR. Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7. Structure. 2009 Nov;17(11):1528–37.

58. Gu L, Fullam A, Brennan R, Schroder M. Human DEAD Box Helicase 3 Couples I B Kinase to Interferon Regulatory Factor 3 Activation. Molecular and Cellular Biology. 2013 May 15;33(10).

59. Fullam A, Gu L, Höhn Y, Schröder M. DDX3 directly facilitates IKKα activation and regulates downstream signalling pathways. Biochemical Journal. 2018 Nov 30;475(22).

60. Yoneyama M, Eisuke Nishida Takashi Fujita, Fukuhara Y, Fukuda M., Nishida E., Fujita T. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. The EMBO Journal. 1998 Feb 15;17(4).

61. Yoneyama M, Suhara W, Fukuhara Y, Sato M, Ozato K, Fujita T. Autocrine Amplification of Type I Interferon Gene Expression Mediated by Interferon Stimulated Gene Factor 3 (ISGF3). Journal of Biochemistry. 1996 Jul 1;120(1).

62. Fullam A, Schröder M. DExD/H-box RNA helicases as mediators of antiviral innate immunity and essential host factors for viral replication. Vol. 1829, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. Elsevier; 2013. p. 854–65.

63. Hou F, Sun L, Zheng H, Skaug B, Jiang Q-X, Chen ZJ. MAVS Forms Functional Prion- like Aggregates to Activate and Propagate Antiviral Innate Immune Response. Cell. 2011 Aug;146(3).

64. Takahasi K, Horiuchi M, Fujii K, Nakamura S, Noda NN, Yoneyama M, et al. Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change. Genes to Cells. 2010 Jul 6;

65. Suhara W, Yoneyama M, Iwamura T, Yoshimura S, Tamura K, Namiki H, et al. Analyses of Virus-Induced Homomeric and Heteromeric Protein Associations between IRF-3 and Coactivator CBP/p300. Journal of Biochemistry. 2000 Aug 1;128(2).

66. Wang P, Zhu S, Yang L, Cui S, Pan W, Jackson R, et al. Nlrp6 regulates intestinal antiviral innate immunity. Science (1979). 2015 Nov 13;350(6262).

67. Liu Y, Lu N, Yuan B, Weng L, Wang F, Liu Y-J, et al. The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells. Cellular & Molecular Immunology. 2014 Jan 16;11(1).

68. Mitoma H, Hanabuchi S, Kim T, Bao M, Zhang Z, Sugimoto N, et al. The DHX33 RNA Helicase Senses Cytosolic RNA and Activates the NLRP3 Inflammasome. Immunity. 2013 Jul;39(1).

69. Sugimoto N, Mitoma H, Kim T, Hanabuchi S, Liu Y-J. Helicase proteins DHX29 and RIG-I cosense cytosolic nucleic acids in the human airway system. Proceedings of the National Academy of Sciences. 2014 May 27;111(21).

70. Zhu Q, Tan P, Li Y, Lin M, Li C, Mao J, et al. DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity. PLOS Pathogens. 2018 Feb 20;14(2).

71. Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA, et al. DDX1, DDX21, and DHX36 Helicases Form a Complex with the Adaptor Molecule TRIF to Sense dsRNA in Dendritic Cells. Immunity. 2011 Jun;34(6).

72. Weaver BK, Kumar KP, Reich NC. Interferon Regulatory Factor 3 and CREB-Binding Protein/p300 Are Subunits of Double-Stranded RNA-Activated Transcription Factor DRAF1. Molecular and Cellular Biology. 1998 Mar 1;18(3).

73. Kumar KP, McBride KM, Weaver BK, Dingwall C, Reich NC. Regulated Nuclear- Cytoplasmic Localization of Interferon Regulatory Factor 3, a Subunit of Double- Stranded RNA-Activated Factor 1. Molecular and Cellular Biology. 2000 Jun 1;20(11).

74. Pyle AM. Translocation and Unwinding Mechanisms of RNA and DNA Helicases. Annual Review of Biophysics. 2008 Jun;37(1).

75. Yedavalli VSRK, Neuveut C, Chi Y, Kleiman L, Jeang K-T. Requirement of DDX3 DEAD Box RNA Helicase for HIV-1 Rev-RRE Export Function. Cell. 2004 Oct;119(3).

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る