Heterogeneous Nuclear Ribonucleoprotein C Proteins Interact with the Human Papillomavirus Type 16 (HPV16) Early 3′-Untranslated Region and Alleviate Suppression of HPV16 Late L1 mRNA Splicing
Autor: | Ann-Kristin Mossberg, Naoko Kajitani, Jacob Glahder, Cecilia Johansson, Stefan Schwartz, Soniya Dhanjal |
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Rok vydání: | 2015 |
Předmět: |
Gene Expression Regulation
Viral Keratinocytes Untranslated region RNA Splicing viruses Blotting Western Fluorescent Antibody Technique Uterine Cervical Neoplasms RNA-binding protein Biology Real-Time Polymerase Chain Reaction Microbiology Biochemistry Gene expression Tumor Cells Cultured Humans Immunoprecipitation RNA Messenger 3' Untranslated Regions neoplasms Molecular Biology Gene Subgenomic mRNA Human papillomavirus 16 integumentary system Reverse Transcriptase Polymerase Chain Reaction Microarray analysis techniques Three prime untranslated region Heterogeneous-Nuclear Ribonucleoprotein Group C virus diseases Oncogene Proteins Viral Cell Biology Microarray Analysis Molecular biology female genital diseases and pregnancy complications Epidermal Cells RNA splicing RNA Viral Capsid Proteins Female Epidermis |
Zdroj: | Journal of Biological Chemistry. 290:13354-13371 |
ISSN: | 0021-9258 |
Popis: | In order to identify cellular factors that regulate human papillomavirus type 16 (HPV16) gene expression, cervical cancer cells permissive for HPV16 late gene expression were identified and characterized. These cells either contained a novel spliced variant of the L1 mRNAs that bypassed the suppressed HPV16 late, 5′-splice site SD3632; produced elevated levels of RNA-binding proteins SRSF1 (ASF/SF2), SRSF9 (SRp30c), and HuR that are known to regulate HPV16 late gene expression; or were shown by a gene expression array analysis to overexpress the RALYL RNA-binding protein of the heterogeneous nuclear ribonucleoprotein C (hnRNP C) family. Overexpression of RALYL or hnRNP C1 induced HPV16 late gene expression from HPV16 subgenomic plasmids and from episomal forms of the full-length HPV16 genome. This induction was dependent on the HPV16 early untranslated region. Binding of hnRNP C1 to the HPV16 early, untranslated region activated HPV16 late 5′-splice site SD3632 and resulted in production of HPV16 L1 mRNAs. Our results suggested that hnRNP C1 controls HPV16 late gene expression. Background: HPV16 late gene expression is suppressed in mitotic cells. Results: hnRNP C proteins bind to the HPV16 early, untranslated region and activate HPV16 late mRNA splicing. Conclusion: hnRNP C proteins control HPV16 late gene expression. Significance: hnRNP C proteins may contribute to the ability of HPV16 to avoid the immune system and establish persistent infections that progress to cancer. |
Databáze: | OpenAIRE |
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