Skip to main content
Protein & Cell logoLink to Protein & Cell
. 2010 Nov 9;1(10):956–964. doi: 10.1007/s13238-010-0117-8

DEXH-Box protein DHX30 is required for optimal function of the zinc-finger antiviral protein

Peiying Ye 1,2, Shufeng Liu 1, Yiping Zhu 1,2, Guifang Chen 1, Guangxia Gao 1,
PMCID: PMC4875121  PMID: 21204022

Abstract

The zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by eliminating viral mRNAs in the cytoplasm. In previous studies, we demonstrated that ZAP directly binds to the viral mRNAs and recruits the RNA exosome to degrade the target RNA. In this article, we provide evidence that a DEXH box RNA helicase, DHX30, is required for optimal antiviral activity of ZAP. Pull-down and co-immunoprecipitation assays demonstrated that DHX30 and ZAP interacted with each other via their N terminal domains. Downregulation of DHX30 with shRNAs reduced ZAP’s antiviral activity. These data implicate that DHX30 is a cellular factor involved in the antiviral function of ZAP.

Keywords: zinc-finger antiviral protein, RNA helicase, DHX30

References

  1. Bick M.J., Carroll J.W., Gao G., Goff S.P., Rice C.M., MacDonald M.R. Expression of the zinc-finger antiviral protein inhibits alphavirus replication. J Virol. 2003;77:11555–11562. doi: 10.1128/JVI.77.21.11555-11562.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen G., Guo X., Lv F., Xu Y., Gao G. p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein. Proc Natl Acad Sci U S A. 2008;105:4352–4357. doi: 10.1073/pnas.0712276105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gao G., Guo X., Goff S.P. Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science. 2002;297:1703–1706. doi: 10.1126/science.1074276. [DOI] [PubMed] [Google Scholar]
  4. Garneau N.L., Wilusz J., Wilusz C.J. The highways and byways of mRNA decay. Nat Rev Mol Cell Biol. 2007;8:113–126. doi: 10.1038/nrm2104. [DOI] [PubMed] [Google Scholar]
  5. Guhaniyogi J., Brewer G. Regulation of mRNA stability in mammalian cells. Gene. 2001;265:11–23. doi: 10.1016/S0378-1119(01)00350-X. [DOI] [PubMed] [Google Scholar]
  6. Guo X., Carroll J.W., Macdonald M.R., Goff S.P., Gao G. The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs. J Virol. 2004;78:12781–12787. doi: 10.1128/JVI.78.23.12781-12787.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guo X., Ma J., Sun J., Gao G. The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proc Natl Acad Sci U S A. 2007;104:151–156. doi: 10.1073/pnas.0607063104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jankowsky E., Fairman M.E. RNA helicases-one fold for many functions. Curr Opin Struct Biol. 2007;17:316–324. doi: 10.1016/j.sbi.2007.05.007. [DOI] [PubMed] [Google Scholar]
  9. Law L.M., Albin O.R., Carroll J.W., Jones C.T., Rice C.M., Macdonald M.R. Identification of a dominant negative inhibitor of human zinc finger antiviral protein reveals a functional endogenous pool and critical homotypic interactions. J Virol. 2010;84:4504–4512. doi: 10.1128/JVI.02018-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liu Q., Greimann J.C., Lima C.D. Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell. 2006;127:1223–1237. doi: 10.1016/j.cell.2006.10.037. [DOI] [PubMed] [Google Scholar]
  11. Muller S., Moller P., Bick M.J., Wurr S., Becker S., Gunther S., Kummerer B.M. Inhibition of filovirus replication by the zinc finger antiviral protein. J Virol. 2007;81:2391–2400. doi: 10.1128/JVI.01601-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Wang Y., Bogenhagen D.F. Human mitochondrial DNA nucleoids are linked to protein folding machinery and metabolic enzymes at the mitochondrial inner membrane. J Biol Chem. 2006;281:25791–25802. doi: 10.1074/jbc.M604501200. [DOI] [PubMed] [Google Scholar]
  13. Zhang Y., Burke C.W., Ryman K.D., Klimstra W.B. Identification and characterization of interferon-induced proteins that inhibit alphavirus replication. J Virol. 2007;81:11246–11255. doi: 10.1128/JVI.01282-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zhou Y., Ma J., Bushan R.B., Wu J.Y., Pan Q., Rong L., Liang C. The packaging of human immunodeficiency virus type 1 RNA is restricted by overexpression of an RNA helicase DHX30. Virology. 2007;372:97–106. doi: 10.1016/j.virol.2007.10.027. [DOI] [PubMed] [Google Scholar]
  15. Zhu Y., Gao G. ZAP-mediated mRNA degradation. RNA Biol. 2008;5:65–67. doi: 10.4161/rna.5.2.6044. [DOI] [PubMed] [Google Scholar]

Articles from Protein & Cell are provided here courtesy of Oxford University Press

RESOURCES