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HPV‐16 E2 contributes to induction of HPV‐16 late gene expression by inhibiting early polyadenylation
Author(s) -
Johansson Cecilia,
Somberg Monika,
Li Xiaoze,
Backström Winquist Ellenor,
Fay Joanna,
Ryan Fergus,
Pim David,
Banks Lawrence,
Schwartz Stefan
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.147
Subject(s) - biology , polyadenylation , gene expression , virology , gene , genetics , regulation of gene expression , microbiology and biotechnology , cancer research
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.