A Novel Function of Human Pumilio Proteins in Cytoplasmic Sensing of Viral Infection

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Mammals utilize innate immune system to counteract viral infections. The host pattern-recognition receptors, such as RIG-I-like receptors (RLRs), sense invading pathogens and initiate innate immune responses. RLRs are composed of three RNA helicases, RIG-I, MDA5 and LGP2, and detect a series of RNA viruses, such as influenza or hepatitis C virus, in the cytoplasm. Upon RNA virus infection, RLRs transmit signals through mitochondrial adaptor protein, IPS-1, to activate transcription factor IRF-3/7, resulting in the production of type I interferon (IFN). Type I IFN plays a crucial role in innate immune system by inducing a hundreds of interferon-stimulated genes and its induction is tightly controlled at transcriptional and translational steps. Pumilio proteins are originally identified as translational repressor through direct binding to specific sequence motifs in the 3′ untranslated regions of specific mRNA, and regulate critical biological processes, such as development and differentiation. In this report, we identified human Pumilio proteins, PUM1 and PUM2, as candidate regulators of IFN signaling. Our results demonstrated an unknown function of Pumilio in viral recognition by LGP2.

Vyšlo v časopise: A Novel Function of Human Pumilio Proteins in Cytoplasmic Sensing of Viral Infection. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004417
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004417

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Zdroje

1. KawaiT, AkiraS (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34 : 637–650.

2. YoneyamaM, FujitaT (2009) RNA recognition and signal transduction by RIG-I-like receptors. Immunological reviews 227 : 54–65.

3. YanN, ChenZJ (2012) Intrinsic antiviral immunity. Nature immunology 13 : 214–222.

4. IretonRC, GaleMJr (2011) RIG-I like receptors in antiviral immunity and therapeutic applications. Viruses 3 : 906–919.

5. SchleeM, HartmannG (2010) The chase for the RIG-I ligand—recent advances. Molecular therapy: the journal of the American Society of Gene Therapy 18 : 1254–1262.

6. YoneyamaM, KikuchiM, NatsukawaT, ShinobuN, ImaizumiT, et al. (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nature immunology 5 : 730–737.

7. YoneyamaM, KikuchiM, MatsumotoK, ImaizumiT, MiyagishiM, et al. (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. Journal of immunology 175 : 2851–2858.

8. WuB, PeisleyA, RichardsC, YaoH, ZengX, et al. (2013) Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell 152 : 276–289.

9. PeisleyA, WuB, YaoH, WalzT, HurS (2013) RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner. Molecular cell 51 : 573–583.

10. XuLG, WangYY, HanKJ, LiLY, ZhaiZ, et al. (2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Molecular cell 19 : 727–740.

11. SethRB, SunL, EaCK, ChenZJ (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122 : 669–682.

12. MeylanE, CurranJ, HofmannK, MoradpourD, BinderM, et al. (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437 : 1167–1172.

13. KawaiT, TakahashiK, SatoS, CobanC, KumarH, et al. (2005) IPS-1, an adaptor triggering RIG-I -⁠ and Mda5-mediated type I interferon induction. Nature immunology 6 : 981–988.

14. KumarH, KawaiT, KatoH, SatoS, TakahashiK, et al. (2006) Essential role of IPS-1 in innate immune responses against RNA viruses. The Journal of experimental medicine 203 : 1795–1803.

15. SunQ, SunL, LiuHH, ChenX, SethRB, et al. (2006) The specific and essential role of MAVS in antiviral innate immune responses. Immunity 24 : 633–642.

16. FitzgeraldKA, McWhirterSM, FaiaKL, RoweDC, LatzE, et al. (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nature immunology 4 : 491–496.

17. SatoM, SuemoriH, HataN, AsagiriM, OgasawaraK, et al. (2000) Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity 13 : 539–548.

18. KatoH, TakeuchiO, SatoS, YoneyamaM, YamamotoM, et al. (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441 : 101–105.

19. KatoH, TakeuchiO, Mikamo-SatohE, HiraiR, KawaiT, et al. (2008) Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. The Journal of experimental medicine 205 : 1601–1610.

20. PichlmairA, SchulzO, TanCP, NaslundTI, LiljestromP, et al. (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314 : 997–1001.

21. HornungV, EllegastJ, KimS, BrzozkaK, JungA, et al. (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314 : 994–997.

22. SchleeM, RothA, HornungV, HagmannCA, WimmenauerV, et al. (2009) Recognition of 5′ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 31 : 25–34.

23. SatohT, KatoH, KumagaiY, YoneyamaM, SatoS, et al. (2010) LGP2 is a positive regulator of RIG-I -⁠ and MDA5-mediated antiviral responses. Proceedings of the National Academy of Sciences of the United States of America 107 : 1512–1517.

24. TakahasiK, KumetaH, TsudukiN, NaritaR, ShigemotoT, et al. (2009) Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. The Journal of biological chemistry 284 : 17465–17474.

25. KatoH, TakahasiK, FujitaT (2011) RIG-I-like receptors: cytoplasmic sensors for non-self RNA. Immunological reviews 243 : 91–98.

26. GackMU, ShinYC, JooCH, UranoT, LiangC, et al. (2007) TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446 : 916–920.

27. GaoD, YangYK, WangRP, ZhouX, DiaoFC, et al. (2009) REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PloS one 4: e5760.

28. OshiumiH, MatsumotoM, HatakeyamaS, SeyaT (2009) Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection. The Journal of biological chemistry 284 : 807–817.

29. ArimotoK, TakahashiH, HishikiT, KonishiH, FujitaT, et al. (2007) Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proceedings of the National Academy of Sciences of the United States of America 104 : 7500–7505.

30. LinR, YangL, NakhaeiP, SunQ, Sharif-AskariE, et al. (2006) Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. The Journal of biological chemistry 281 : 2095–2103.

31. KayagakiN, PhungQ, ChanS, ChaudhariR, QuanC, et al. (2007) DUBA: a deubiquitinase that regulates type I interferon production. Science 318 : 1628–1632.

32. FriedmanCS, O'DonnellMA, Legarda-AddisonD, NgA, CardenasWB, et al. (2008) The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO reports 9 : 930–936.

33. JiangX, KinchLN, BrautigamCA, ChenX, DuF, et al. (2012) Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity 36 : 959–973.

34. OnomotoK, JogiM, YooJS, NaritaR, MorimotoS, et al. (2012) Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PloS one 7: e43031.

35. NgCS, JogiM, YooJS, OnomotoK, KoikeS, et al. (2013) Encephalomyocarditis virus disrupts stress granules, the critical platform for triggering antiviral innate immune responses. Journal of virology 87 : 9511–9522.

36. FungG, NgCS, ZhangJ, ShiJ, WongJ, et al. (2013) Production of a dominant-negative fragment due to G3BP1 cleavage contributes to the disruption of mitochondria-associated protective stress granules during CVB3 infection. PloS one 8: e79546.

37. YooJS, TakahasiK, NgCS, OudaR, OnomotoK, et al. (2014) DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation. PLoS pathogens 10: e1004012.

38. MurataY, WhartonRP (1995) Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos. Cell 80 : 747–756.

39. ForbesA, LehmannR (1998) Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells. Development 125 : 679–690.

40. ParisiM, LinH (1999) The Drosophila pumilio gene encodes two functional protein isoforms that play multiple roles in germline development, gonadogenesis, oogenesis and embryogenesis. Genetics 153 : 235–250.

41. DubnauJ, ChiangAS, GradyL, BarditchJ, GossweilerS, et al. (2003) The staufen/pumilio pathway is involved in Drosophila long-term memory. Current biology: CB 13 : 286–296.

42. ChenD, ZhengW, LinA, UyhaziK, ZhaoH, et al. (2012) Pumilio 1 suppresses multiple activators of p53 to safeguard spermatogenesis. Current biology: CB 22 : 420–425.

43. WangX, McLachlanJ, ZamorePD, HallTM (2002) Modular recognition of RNA by a human pumilio-homology domain. Cell 110 : 501–512.

44. FriendK, CampbellZT, CookeA, Kroll-ConnerP, WickensMP, et al. (2012) A conserved PUF-Ago-eEF1A complex attenuates translation elongation. Nature structural & molecular biology 19 : 176–183.

45. VesseyJP, VaccaniA, XieY, DahmR, KarraD, et al. (2006) Dendritic localization of the translational repressor Pumilio 2 and its contribution to dendritic stress granules. The Journal of neuroscience: the official journal of the Society for Neuroscience 26 : 6496–6508.

46. SaitoT, HiraiR, LooYM, OwenD, JohnsonCL, et al. (2007) Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proceedings of the National Academy of Sciences of the United States of America 104 : 582–587.

47. HuhSU, KimMJ, PaekKH (2013) Arabidopsis Pumilio protein APUM5 suppresses Cucumber mosaic virus infection via direct binding of viral RNAs. Proceedings of the National Academy of Sciences of the United States of America 110 : 779–784.

48. MoriM, YoneyamaM, ItoT, TakahashiK, InagakiF, et al. (2004) Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. The Journal of biological chemistry 279 : 9698–9702.

49. TakahasiK, YoneyamaM, NishihoriT, HiraiR, KumetaH, et al. (2008) Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Molecular cell 29 : 428–440.