title: Control of human papillomavirus gene expression by alternative splicing.
abstract: Human papillomaviruses possess circular double stranded DNA genomes of around 8kb in size from which multiple mRNAs are synthesized during an infectious life cycle. Although at least three viral promoters are used to initiate transcription, viral mRNAs are largely the product of processing of pre-mRNAs by alternative splicing and polyadenylation. The HPV life cycle and viral gene expression are tightly linked to differentiation of the epithelium the virus infects: there is an orchestrated production of viral mRNAs and proteins. In this review we describe viral mRNA expression and the roles of the SR and hnRNP proteins that respectively positively and negatively regulate splicing. We discuss HPV regulation of splicing factors and detail the evidence that the papillomavirus E2 protein has splicing-related activities. We highlight the possibility that HPV-mediated control of splicing in differentiating epithelial cells may be necessary to accomplish the viral replication cycle.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research; Institute of Infection, Immunity and Inflammation; College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow G61 1QH, Scotland, UK. Electronic address: Sheila.Graham@gla.ac.uk.
authors.forename: Sheila V
authors.initials: SV
authors.lastname: Graham
authors.affiliation: MRC-University of Glasgow Centre for Virus Research; Institute of Infection, Immunity and Inflammation; College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow G61 1QH, Scotland, UK.
authors.forename: Arwa Ali A
authors.initials: AAA
authors.lastname: Faizo
mesh_terms: D017398:Alternative Splicing; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D000068103:Serine-Arginine Splicing Factors
keywords: Alternative splicing; E2; Human papillomavirus; Life cycle; SR protein; hnRNP