A Downstream Polyadenylation Element in Human Papillomavirus Type 16 L2 Encodes Multiple GGG Motifs and Interacts with hnRNP H
2005 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 79, no 14, 9254-9269 p.Article in journal (Refereed) Published
Production of human papillomavirus type 16 (HPV-16) virus particles is totally dependent on the differentiation-dependent induction of viral L1 and L2 late gene expression. The early polyadenylation signal in HPV-16 plays a major role in the switch from the early to the late, productive stage of the viral life cycle. Here, we show that the L2 coding region of HPV-16 contains RNA elements that are necessary for polyadenylation at the early polyadenylation signal. Consecutive mutations in six GGG motifs located 174 nucleotides downstream of the polyadenylation signal resulted in a gradual decrease in polyadenylation at the early polyadenylation signal. This caused read-through into the late region, followed by production of the late mRNAs encoding L1 and L2. Binding of hnRNP H to the various triple-G mutants correlated with functional activity of the HPV-16 early polyadenylation signal. In addition, the polyadenylation factor CStF-64 was also found to interact specifically with the region in L2 located 174 nucleotides downstream of the early polyadenylation signal. Staining of cervix epithelium with anti-hnRNP H-specific antiserum revealed high expression levels of hnRNP H in the lower layers of cervical epithelium and a loss of hnRNP H production in the superficial layers, supporting a model in which a differentiation-dependent down regulation of hnRNP H causes a decrease in HPV-16 early polyadenylation and an induction of late gene expression.
Place, publisher, year, edition, pages
2005. Vol. 79, no 14, 9254-9269 p.
Base Sequence, Capsid Proteins/*genetics, Cell Differentiation, Cervix Uteri/cytology/metabolism, Female, Hela Cells, Heterogeneous-Nuclear Ribonucleoprotein Group F-H/*physiology, Humans, Molecular Sequence Data, Oncogene Proteins; Viral/*genetics, Open Reading Frames, Polyadenylation, RNA/metabolism, RNA Splicing, Research Support; Non-U.S. Gov't
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-92574DOI: 10.1128/JVI.79.14.9254-9269.2005PubMedID: 15994820OAI: oai:DiVA.org:uu-92574DiVA: diva2:165708