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
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