Serine/arginine-rich protein 30c activates human papillomavirus type 16 L1 mRNA expression via a bimodal mechanism Free

Abstract

Two splice sites on the human papillomavirus type 16 (HPV-16) genome are used exclusively by the late capsid protein L1 mRNAs: SD3632 and SA5639. These splice sites are suppressed in mitotic cells. This study showed that serine/arginine-rich protein 30c (SRp30c), also named SFRS9, activated both SD3632 and SA5639 and induced production of L1 mRNA. Activation of HPV-16 L1 mRNA splicing by SRp30c required an intact arginine/serine-repeat (RS) domain of SRp30c. In addition to this effect, SRp30c could enhance L1 mRNA production indirectly by inhibiting the early 3′-splice site SA3358, which competed with the late 3′-splice site SA5639. SRp30c bound directly to sequences downstream of SA3358, suggesting that SRp30c inhibited the enhancer at SA3358 and caused a redirection of splicing to the late 3′-splice site SA5639. This inhibitory effect of SRp30c was independent of its RS domain. These results suggest that SRp30c can activate HPV-16 L1 mRNA expression via a bimodal mechanism: directly by stimulating splicing to late splice sites and indirectly by inhibiting competing early splice sites.

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2011-10-01
2024-03-29
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References

  1. Baker C., Calef C. 1997; Maps of papillomavirus mRNA transcripts. In Human Papillomaviruses: a Compilation and Analysis of Nucleic Acid and Amino Acid Sequences Edited by Billakanti S. R., Calef C. E., Farmer A. D., Halpern A. L., Myers G. L. Los Alamos, NM: Los Alamos National Laboratory;
    [Google Scholar]
  2. Collier B., Goobar-Larsson L., Sokolowski M., Schwartz S. 1998; Translational inhibition in vitro of human papillomavirus type 16 L2 mRNA mediated through interaction with heterogenous ribonucleoprotein K and poly(rC)-binding proteins 1 and 2. J Biol Chem 273:22648–22656 [View Article][PubMed]
    [Google Scholar]
  3. Collier B., Öberg D., Zhao X., Schwartz S. 2002; Specific inactivation of inhibitory sequences in the 5′ end of the human papillomavirus type 16 L1 open reading frame results in production of high levels of L1 protein in human epithelial cells. J Virol 76:2739–2752 [View Article][PubMed]
    [Google Scholar]
  4. Cumming S. A., Repellin C. E., McPhillips M., Radford J. C., Clements J. B., Graham S. V. 2002; The human papillomavirus type 31 late 3′ untranslated region contains a complex bipartite negative regulatory element. J Virol 76:5993–6003 [View Article][PubMed]
    [Google Scholar]
  5. Doorbar J. 2005; The papillomavirus life cycle. J Clin Virol 32:Suppl. 1S7–S15 [View Article][PubMed]
    [Google Scholar]
  6. Estmer Nilsson C., Petersen-Mahrt S., Durot C., Shtrichman R., Krainer A. R., Kleinberger T., Akusjärvi G. 2001; The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins. EMBO J 20:864–871 [View Article][PubMed]
    [Google Scholar]
  7. Fay J., Kelehan P., Lambkin H., Schwartz S. 2009; Increased expression of cellular RNA-binding proteins in HPV-induced neoplasia and cervical cancer. J Med Virol 81:897–907 [View Article][PubMed]
    [Google Scholar]
  8. Goraczniak R., Gunderson S. I. 2008; The regulatory element in the 3′-untranslated region of human papillomavirus 16 inhibits expression by binding CUG-binding protein 1. J Biol Chem 283:2286–2296 [View Article][PubMed]
    [Google Scholar]
  9. Graham S. V. 2008; Papillomavirus 3′ UTR regulatory elements. Front Biosci 13:5646–5663 [View Article][PubMed]
    [Google Scholar]
  10. Howley P. M., Lowy D. R. 2001; Papillomaviruses and their replication. In Fields Virology, 4th edn. pp. 2197–2229 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  11. Huang T. S., Nilsson C. E., Punga T., Akusjärvi G. 2002; Functional inactivation of the SR family of splicing factors during a vaccinia virus infection. EMBO Rep 3:1088–1093 [View Article][PubMed]
    [Google Scholar]
  12. Jia R., Liu X., Tao M., Kruhlak M., Guo M., Meyers C., Baker C. C., Zheng Z. M. 2009; Control of the papillomavirus early-to-late switch by differentially expressed SRp20. J Virol 83:167–180 [View Article][PubMed]
    [Google Scholar]
  13. Johansson C., Zhao H., Bajak E., Granberg F., Pettersson U., Svensson C. 2005; Impact of the interaction between adenovirus E1A and CtBP on host cell gene expression. Virus Res 113:51–63 [View Article][PubMed]
    [Google Scholar]
  14. Kanopka A., Mühlemann O., Akusjärvi G. 1996; Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA. Nature 381:535–538 [View Article][PubMed]
    [Google Scholar]
  15. Kanopka A., Mühlemann O., Petersen-Mahrt S., Estmer C., Öhrmalm C., Akusjärvi G. 1998; Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins. Nature 393:185–187 [View Article][PubMed]
    [Google Scholar]
  16. Koffa M. D., Graham S. V., Takagaki Y., Manley J. L., Clements J. B. 2000; The human papillomavirus type 16 negative regulatory RNA element interacts with three proteins that act at different posttranscriptional levels. Proc Natl Acad Sci U S A 97:4677–4682 [View Article][PubMed]
    [Google Scholar]
  17. Longworth M. S., Laimins L. A. 2004; Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Mol Biol Rev 68:362–372 [View Article][PubMed]
    [Google Scholar]
  18. McPhillips M. G., Veerapraditsin T., Cumming S. A., Karali D., Milligan S. G., Boner W., Morgan I. M., Graham S. V. 2004; SF2/ASF binds the human papillomavirus type 16 late RNA control element and is regulated during differentiation of virus-infected epithelial cells. J Virol 78:10598–10605 [View Article][PubMed]
    [Google Scholar]
  19. Milligan S. G., Veerapraditsin T., Ahamet B., Mole S., Graham S. V. 2007; Analysis of novel human papillomavirus type 16 late mRNAs in differentiated W12 cervical epithelial cells. Virology 360:172–181 [View Article][PubMed]
    [Google Scholar]
  20. Oberg D., Collier B., Zhao X., Schwartz S. 2003; Mutational inactivation of two distinct negative RNA elements in the human papillomavirus type 16 L2 coding region induces production of high levels of L2 in human cells. J Virol 77:11674–11684 [View Article][PubMed]
    [Google Scholar]
  21. Oberg D., Fay J., Lambkin H., Schwartz S. 2005; A downstream polyadenylation element in human papillomavirus type 16 L2 encodes multiple GGG motifs and interacts with hnRNP H. J Virol 79:9254–9269 [View Article][PubMed]
    [Google Scholar]
  22. Raffetseder U., Frye B., Rauen T., Jürchott K., Royer H.-D., Jansen P. L., Mertens P. R. 2003; Splicing factor SRp30c interaction with Y-box protein-1 confers nuclear YB-1 shuttling and alternative splice site selection. J Biol Chem 278:18241–18248 [View Article][PubMed]
    [Google Scholar]
  23. Rush M., Zhao X., Schwartz S. 2005; A splicing enhancer in the E4 coding region of human papillomavirus type 16 is required for early mRNA splicing and polyadenylation as well as inhibition of premature late gene expression. J Virol 79:12002–12015 [View Article][PubMed]
    [Google Scholar]
  24. Schwartz S. 2008; HPV-16 RNA processing. Front Biosci 13:5880–5891 [View Article][PubMed]
    [Google Scholar]
  25. Skalweit A., Doller A., Huth A., Kähne T., Persson P. B., Thiele B. J. 2003; Posttranscriptional control of renin synthesis: identification of proteins interacting with renin mRNA 3′-untranslated region. Circ Res 92:419–427 [View Article][PubMed]
    [Google Scholar]
  26. Sokolowski M., Schwartz S. 2001; Heterogeneous nuclear ribonucleoprotein C binds exclusively to the functionally important UUUUU-motifs in the human papillomavirus type-1 AU-rich inhibitory element. Virus Res 73:163–175 [View Article][PubMed]
    [Google Scholar]
  27. Sokolowski M., Zhao C., Tan W., Schwartz S. 1997; AU-rich mRNA instability elements on human papillomavirus type 1 late mRNAs and c-fos mRNAs interact with the same cellular factors. Oncogene 15:2303–2319 [View Article][PubMed]
    [Google Scholar]
  28. Sokolowski M., Furneaux H., Schwartz S. 1999; The inhibitory activity of the AU-rich RNA element in the human papillomavirus type 1 late 3′ untranslated region correlates with its affinity for the elav-like HuR protein. J Virol 73:1080–1091[PubMed]
    [Google Scholar]
  29. Somberg M., Schwartz S. 2010; Multiple ASF/SF2 sites in the human papillomavirus type 16 (HPV-16) E4-coding region promote splicing to the most commonly used 3′-splice site on the HPV-16 genome. J Virol 84:8219–8230 [View Article][PubMed]
    [Google Scholar]
  30. Somberg M., Zhao X., Fröhlich M., Evander M., Schwartz S. 2008; Polypyrimidine tract binding protein induces human papillomavirus type 16 late gene expression by interfering with splicing inhibitory elements at the major late 5′ splice site, SD3632. J Virol 82:3665–3678 [View Article][PubMed]
    [Google Scholar]
  31. Somberg M., Rush M., Fay J., Ryan F., Lambkin H., Akusjärvi G., Schwartz S. 2009; Adenovirus E4orf4 induces HPV-16 late L1 mRNA production. Virology 383:279–290 [View Article][PubMed]
    [Google Scholar]
  32. Terhune S. S., Hubert W. G., Thomas J. T., Laimins L. A. 2001; Early polyadenylation signals of human papillomavirus type 31 negatively regulate capsid gene expression. J Virol 75:8147–8157 [View Article][PubMed]
    [Google Scholar]
  33. Tranell A., Fenyö E. M., Schwartz S. 2010; Serine- and arginine-rich proteins 55 and 75 (SRp55 and SRp75) induce production of HIV-1 vpr mRNA by inhibiting the 5′-splice site of exon 3. J Biol Chem 285:31537–31547 [View Article][PubMed]
    [Google Scholar]
  34. Wiklund L., Sokolowski M., Carlsson A., Rush M., Schwartz S. 2002; Inhibition of translation by UAUUUAU and UAUUUUUAU motifs of the AU-rich RNA instability element in the HPV-1 late 3′ untranslated region. J Biol Chem 277:40462–40471 [View Article][PubMed]
    [Google Scholar]
  35. Zhao X., Rush M., Schwartz S. 2004; Identification of an hnRNP A1-dependent splicing silencer in the human papillomavirus type 16 L1 coding region that prevents premature expression of the late L1 gene. J Virol 78:10888–10905 [View Article][PubMed]
    [Google Scholar]
  36. Zhao X., Öberg D., Rush M., Fay J., Lambkin H., Schwartz S. 2005; A 57-nucleotide upstream early polyadenylation element in human papillomavirus type 16 interacts with hFip1, CstF-64, hnRNP C1/C2, and polypyrimidine tract binding protein. J Virol 79:4270–4288 [View Article][PubMed]
    [Google Scholar]
  37. Zhao X., Rush M., Carlsson A., Schwartz S. 2007; The presence of inhibitory RNA elements in the late 3′-untranslated region is a conserved property of human papillomaviruses. Virus Res 125:135–144 [View Article][PubMed]
    [Google Scholar]
  38. Zheng Z. M., Baker C. C. 2006; Papillomavirus genome structure, expression, and post-transcriptional regulation. Front Biosci 11:2286–2302 [View Article][PubMed]
    [Google Scholar]
  39. zur Hausen H. 2002; Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350 [View Article][PubMed]
    [Google Scholar]
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