The Role of Polyadenylation in Human Papillomavirus Type 16 Late Gene Expression

High-risk type human papillomaviruses (HPVs) are associated with cancer. HPVs are strictly epitheliotropic and infect basal cell layers, establishing a life cycle strongly linked to the differentiation stage of the infected cells. The viral capsid late genes, L2 and L1, are only expressed in terminally differentiated epithelium. Late gene expression involves regulation of most gene processing events including transcription, splicing, polyadenylation, mRNA stability and translation.Both L2 and L1 have elements present in the open reading frames (ORFs) negatively affecting mRNA levels and translation. The negative elements in L1 were mapped to the first 514 nucleotides, with the strongest inhibitory effect located in the first 129 nucleotides. The negative elements in the L2 sequence were concentrated in two locations on the gene. Both genes were mutated by changing the nucleotide sequence while retaining the amino acid sequence. Mutating the first 514 nucleotides in L1 deactivated the negative elements while the entire L2 gene had to be mutated to achieve the same result. The L2 protein was found to localise the L1 protein into a punctuated pattern in the nucleus.In the HPV-16 genome the negative elements reside in regions important for regulation of polyadenylation and splicing, critical for late gene expression. By exchanging parts of the L2 gene…


1 Introduction
1.1 Virology
1.2 History of papillomaviruses
1.3 Human papillomaviruses and cancer
1.4 Human papillomavirus structure
1.5 Papillomavirus life cycle
1.6 Human papillomaviruses and gene expression
1.7 Long control-, early- and late region genomic structure and function
1.7.1 LCR
1.7.2 The early region E2 and E1 E6 and E7 E5 function and immune defence E4
1.7.3 The late region
1.8 Gene expression
1.8.1 Capping
1.8.2 Polyadenylation
1.8.3 Splicing
1.8.4 The exon definition model
1.8.5 Linking mRNA processing and transcription
1.8.6 Nuclear export of mRNA
1.8.7 Translation
1.8.8 Regulation of mRNA polyadenylation
1.8.9 Papillomavirus and late polyadenylation
1.8.10 Papillomavirus early polyadenylation
1.8.11 Negative elements
2 Introduction to papers
2.1 Paper I (45)
4.2 Paper II (222)
2.3 Paper III (223)
3. Future perspectives
4. Popularvetenskaplig sammanfattning (In Swedish)
5 Acknowledgement
6 References

Author:  Oberg, Daniel

Source: Uppsala University Library

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