1887

Abstract

Retroviral transcripts have cis-acting elements that interact with host and viral proteins to enable efficient nuclear export and/or translation; however, it is poorly understood whether the transcripts of human endogenous retroviral genes retain such elements. Here, we show that human syncytin-1, which is derived from human endogenous retrovirus W, requires a 3′ untranslated region (3′UTR) for efficient gene expression and retains a post-transcriptional regulatory element (named SPRE). The insertion of SPRE markedly increased a reporter gene (human immunodeficiency virus type 1 Gag) expression without affecting the amounts of nuclear or cytoplasmic transcript. Deletion analysis identified a required sequence for SPRE activity, and the prediction of the RNA secondary structure demonstrated a common secondary structure found among active SPRE sequences. Another human syncytin, syncytin-2, also requires a 3′UTR for efficient gene expression. These data provide insights into post-transcriptional regulation in endogenous retroviral gene expression.

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2019-02-22
2019-08-23
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References

  1. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860–921 [CrossRef][PubMed]
    [Google Scholar]
  2. Denner J. Expression and function of endogenous retroviruses in the placenta. APMIS 2016;124:31–43 [CrossRef][PubMed]
    [Google Scholar]
  3. Mi S, Lee X, Li X, Veldman GM, Finnerty H et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000;403:785–789 [CrossRef][PubMed]
    [Google Scholar]
  4. Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G et al. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 2000;74:3321–3329 [CrossRef][PubMed]
    [Google Scholar]
  5. Blaise S, de Parseval N, Bénit L, Heidmann T. Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci USA 2003;100:13013–13018 [CrossRef][PubMed]
    [Google Scholar]
  6. Mallet F, Bouton O, Prudhomme S, Cheynet V, Oriol G et al. The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. Proc Natl Acad Sci USA 2004;101:1731–1736 [CrossRef][PubMed]
    [Google Scholar]
  7. Esnault C, Cornelis G, Heidmann O, Heidmann T. Differential evolutionary fate of an ancestral primate endogenous retrovirus envelope gene, the EnvV syncytin, captured for a function in placentation. PLoS Genet 2013;9:e10034001003412 [CrossRef][PubMed]
    [Google Scholar]
  8. Dupressoir A, Marceau G, Vernochet C, Bénit L, Kanellopoulos C et al. Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proc Natl Acad Sci USA 2005;102:725–730 [CrossRef][PubMed]
    [Google Scholar]
  9. Heidmann O, Vernochet C, Dupressoir A, Heidmann T. Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new "syncytin" in a third order of mammals. Retrovirology 2009;6:1–11 [CrossRef]
    [Google Scholar]
  10. Cornelis G, Heidmann O, Bernard-Stoecklin S, Reynaud K, Véron G et al. Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora. Proc Natl Acad Sci USA 2012;109:E432E441 [CrossRef][PubMed]
    [Google Scholar]
  11. Cornelis G, Heidmann O, Degrelle SA, Vernochet C, Lavialle C et al. Captured retroviral envelope syncytin gene associated with the unique placental structure of higher ruminants. Proc Natl Acad Sci USA 2013;110:E828E837 [CrossRef][PubMed]
    [Google Scholar]
  12. Nakaya Y, Koshi K, Nakagawa S, Hashizume K, Miyazawa T. Fematrin-1 is involved in fetomaternal cell-to-cell fusion in Bovinae placenta and has contributed to diversity of ruminant placentation. J Virol 2013;87:10563–10572 [CrossRef][PubMed]
    [Google Scholar]
  13. Cornelis G, Vernochet C, Carradec Q, Souquere S, Mulot B et al. Retroviral envelope gene captures and syncytin exaptation for placentation in marsupials. Proc Natl Acad Sci USA 2015;112:E487E496 [CrossRef][PubMed]
    [Google Scholar]
  14. Huang Q, Chen H, Li J, Oliver M, Ma X et al. Epigenetic and non-epigenetic regulation of syncytin-1 expression in human placenta and cancer tissues. Cell Signal 2014;26:648–656 [CrossRef][PubMed]
    [Google Scholar]
  15. Sandri-Goldin RM. Viral regulation of mRNA export. J Virol 2004;78:4389–4396 [CrossRef][PubMed]
    [Google Scholar]
  16. Bray M, Prasad S, Dubay JW, Hunter E, Jeang KT et al. A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci USA 1994;91:1256–1260 [CrossRef]
    [Google Scholar]
  17. Pasquinelli AE, Ernst RK, Lund E, Grimm C, Zapp ML et al. The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. EMBO J 1997;16:7500–7510 [CrossRef][PubMed]
    [Google Scholar]
  18. Grüter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C et al. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell 1998;1:649–659 [CrossRef]
    [Google Scholar]
  19. Sinha A, Johnson WE. Retroviruses of the RDR superinfection interference group: ancient origins and broad host distribution of a promiscuous Env gene. Curr Opin Virol 2017;25:105–112 [CrossRef][PubMed]
    [Google Scholar]
  20. Sakuma T, Davila JI, Malcolm JA, Kocher JP, Tonne JM et al. Murine leukemia virus uses NXF1 for nuclear export of spliced and unspliced viral transcripts. J Virol 2014;88:4069–4082 [CrossRef][PubMed]
    [Google Scholar]
  21. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 2003;31:3406–3415 [CrossRef][PubMed]
    [Google Scholar]
  22. Jin L, Guzik BW, Bor YC, Rekosh D, Hammarskjöld ML. Tap and NXT promote translation of unspliced mRNA. Genes Dev 2003;17:3075–3086 [CrossRef][PubMed]
    [Google Scholar]
  23. Blond JL, Besème F, Duret L, Bouton O, Bedin F et al. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J Virol 1999;73:1175–1185[PubMed]
    [Google Scholar]
  24. Tabernero C, Zolotukhin AS, Valentin A, Pavlakis GN, Felber BK. The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function. J Virol 1996;70:5998–6011[PubMed]
    [Google Scholar]
  25. Teplova M, Wohlbold L, Khin NW, Izaurralde E, Patel DJ. Structure-function studies of nucleocytoplasmic transport of retroviral genomic RNA by mRNA export factor TAP. Nat Struct Mol Biol 2011;18:990–998 [CrossRef][PubMed]
    [Google Scholar]
  26. Perelman P, Johnson WE, Roos C, Seuánez HN, Horvath JE et al. A molecular phylogeny of living primates. PLoS Genet 2011;7:e100134217 [CrossRef][PubMed]
    [Google Scholar]
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