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HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting early polyadenylation.

Johansson, Cecilia LU ; Somberg, Monika; Li, Xiaoze LU ; Winquist, Ellenor LU ; Fay, Joanna; Ryan, Fergus; Pim, David; Banks, Lawrence and Schwartz, Stefan LU (2012) In EMBO Journal 31(14). p.3212-3227
Abstract
We provide evidence that the human papillomavirus (HPV) E2 protein regulates HPV late gene expression. High levels of E2 caused a read-through at the early polyadenylation signal pAE into the late region of the HPV genome, thereby inducing expression of L1 and L2 mRNAs. This is a conserved property of E2 of both mucosal and cutaneous HPV types. Induction could be reversed by high levels of HPV-16 E1 protein, or by the polyadenylation factor CPSF30. HPV-16 E2 inhibited polyadenylation in vitro by preventing the assembly of the CPSF complex. Both the N-terminal and hinge domains of E2 were required for induction of HPV late gene expression in transfected cells as well as for inhibition of polyadenylation in vitro. Finally, overexpression of... (More)
We provide evidence that the human papillomavirus (HPV) E2 protein regulates HPV late gene expression. High levels of E2 caused a read-through at the early polyadenylation signal pAE into the late region of the HPV genome, thereby inducing expression of L1 and L2 mRNAs. This is a conserved property of E2 of both mucosal and cutaneous HPV types. Induction could be reversed by high levels of HPV-16 E1 protein, or by the polyadenylation factor CPSF30. HPV-16 E2 inhibited polyadenylation in vitro by preventing the assembly of the CPSF complex. Both the N-terminal and hinge domains of E2 were required for induction of HPV late gene expression in transfected cells as well as for inhibition of polyadenylation in vitro. Finally, overexpression of HPV-16 E2 induced late gene expression from a full-length genomic clone of HPV-16. We speculate that the accumulation of high levels of E2 during the viral life cycle, not only turns off the expression of the pro-mitotic viral E6 and E7 genes, but also induces the expression of the late HPV genes L1 and L2. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
EMBO Journal
volume
31
issue
14
pages
3212 - 3227
publisher
Oxford University Press
external identifiers
  • wos:000306524900015
  • pmid:22617423
  • scopus:84864126434
ISSN
1460-2075
DOI
10.1038/emboj.2012.147
language
English
LU publication?
yes
id
17ebb22e-a0b5-4ca3-8078-f73ecc470d66 (old id 2608589)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22617423?dopt=Abstract
date added to LUP
2012-06-03 20:59:42
date last changed
2017-11-12 03:40:07
@article{17ebb22e-a0b5-4ca3-8078-f73ecc470d66,
  abstract     = {We provide evidence that the human papillomavirus (HPV) E2 protein regulates HPV late gene expression. High levels of E2 caused a read-through at the early polyadenylation signal pAE into the late region of the HPV genome, thereby inducing expression of L1 and L2 mRNAs. This is a conserved property of E2 of both mucosal and cutaneous HPV types. Induction could be reversed by high levels of HPV-16 E1 protein, or by the polyadenylation factor CPSF30. HPV-16 E2 inhibited polyadenylation in vitro by preventing the assembly of the CPSF complex. Both the N-terminal and hinge domains of E2 were required for induction of HPV late gene expression in transfected cells as well as for inhibition of polyadenylation in vitro. Finally, overexpression of HPV-16 E2 induced late gene expression from a full-length genomic clone of HPV-16. We speculate that the accumulation of high levels of E2 during the viral life cycle, not only turns off the expression of the pro-mitotic viral E6 and E7 genes, but also induces the expression of the late HPV genes L1 and L2.},
  author       = {Johansson, Cecilia and Somberg, Monika and Li, Xiaoze and Winquist, Ellenor and Fay, Joanna and Ryan, Fergus and Pim, David and Banks, Lawrence and Schwartz, Stefan},
  issn         = {1460-2075},
  language     = {eng},
  number       = {14},
  pages        = {3212--3227},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {HPV-16 E2 contributes to induction of HPV-16 late gene expression by inhibiting early polyadenylation.},
  url          = {http://dx.doi.org/10.1038/emboj.2012.147},
  volume       = {31},
  year         = {2012},
}