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hnRNP L controls HPV16 RNA polyadenylation and splicing in an Akt kinase-dependent manner

Kajitani, Naoko LU ; Glahder, Jacob LU ; Wu, Chengjun; Yu, Haoran LU ; Nilsson, Kersti LU and Schwartz, Stefan LU (2017) In Nucleic Acids Research 45(16). p.9654-9678
Abstract

Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified 'hot spots' for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs. Furthermore, siRNA knock-down of hnRNP L or Akt induced HPV16 gene expression. Treatment of HPV16 immortalized keratinocytes with Akt kinase inhibitor reduced hnRNP... (More)

Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified 'hot spots' for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs. Furthermore, siRNA knock-down of hnRNP L or Akt induced HPV16 gene expression. Treatment of HPV16 immortalized keratinocytes with Akt kinase inhibitor reduced hnRNP L binding to HPV16 mRNAs and induced HPV16 L1 mRNA production. Finally, deletion of the hnRNP L binding sites in HPV16 subgenomic expression plasmids resulted in activation of HPV16 late gene expression. In conclusion, the Akt kinase inhibits HPV16 late gene expression at the level of RNA processing by controlling the RNA-binding protein hnRNP L. We speculate that Akt kinase activity upholds an intracellular milieu that favours HPV16 early gene expression and suppresses HPV16 late gene expression.

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organization
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type
Contribution to journal
publication status
published
subject
in
Nucleic Acids Research
volume
45
issue
16
pages
25 pages
publisher
Oxford University Press
external identifiers
  • scopus:85031939369
  • wos:000411096400038
ISSN
1362-4962
DOI
10.1093/nar/gkx606
language
English
LU publication?
yes
id
37d757b9-231e-4582-a736-ea423e7f0ef2
date added to LUP
2017-10-30 14:59:38
date last changed
2018-03-25 04:40:47
@article{37d757b9-231e-4582-a736-ea423e7f0ef2,
  abstract     = {<p>Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified 'hot spots' for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs. Furthermore, siRNA knock-down of hnRNP L or Akt induced HPV16 gene expression. Treatment of HPV16 immortalized keratinocytes with Akt kinase inhibitor reduced hnRNP L binding to HPV16 mRNAs and induced HPV16 L1 mRNA production. Finally, deletion of the hnRNP L binding sites in HPV16 subgenomic expression plasmids resulted in activation of HPV16 late gene expression. In conclusion, the Akt kinase inhibits HPV16 late gene expression at the level of RNA processing by controlling the RNA-binding protein hnRNP L. We speculate that Akt kinase activity upholds an intracellular milieu that favours HPV16 early gene expression and suppresses HPV16 late gene expression.</p>},
  author       = {Kajitani, Naoko and Glahder, Jacob and Wu, Chengjun and Yu, Haoran and Nilsson, Kersti and Schwartz, Stefan},
  issn         = {1362-4962},
  language     = {eng},
  month        = {09},
  number       = {16},
  pages        = {9654--9678},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {hnRNP L controls HPV16 RNA polyadenylation and splicing in an Akt kinase-dependent manner},
  url          = {http://dx.doi.org/10.1093/nar/gkx606},
  volume       = {45},
  year         = {2017},
}