Human papillomavirus type 31b late gene expression is regulated through protein kinase C-mediated changes in RNA processing - PubMed (original) (raw)
Human papillomavirus type 31b late gene expression is regulated through protein kinase C-mediated changes in RNA processing
M Hummel et al. J Virol. 1995 Jun.
Abstract
Expression of the human papillomavirus (HPV) capsid genes, L1 and L2, as well as amplification of viral DNA and virion assembly occur in the terminally differentiated layers of infected stratified squamous epithelium in vivo. These processes can be duplicated in the laboratory through the use of organotypic or raft cultures. When CIN612 cells, which contain episomal copies of the high-risk HPV type 31b, are allowed to differentiate in raft cultures, the expression of transcripts encoding the early genes E1--E4 and E5 is induced. These transcripts are initiated at the differentiation-dependent P742 promoter located in the middle of the E7 open reading frame. Exposure of raft cultures to activators of protein kinase C, such as phorbol esters, results in the further induction of late gene expression as well as virion assembly. In this study, we have investigated the mechanism by which activators of protein kinase C induce late gene expression. The major L1 transcript was found to be encoded by a bicistronic E1--E4, L1 RNA which initiated at the differentiation-dependent promoter P742. Additional low-level expression of L1-containing RNAs was also observed from the early-region promoter, P97. The major L2 transcripts were found to be encoded by E1--E4, E5, L2, L1 RNAs which were also initiated in the early region, probably at the differentiation-specific promoter P742. While early and late RNAs were found to be expressed from the same promoter, they differed in utilization of splicing and polyadenylation sites. Raft cultures treated with activators of protein kinase C induced expression of late genes, but no change in the abundance of early RNAs initiated at the P742 promoter was observed. Thus, the increase in late gene expression was likely due to changes in RNA processing or stabilization rather than an increase in the rate of transcription from P742. Regulation of HPV late gene expression therefore occurs at two levels: differentiation-dependent induction of the P742 promoter, which can be mimicked in vitro by growth in raft cultures, and posttranscriptional changes that can be induced by activation of protein kinase C. These posttranscriptional changes may occur through inactivation or down-regulation of splicing factors which inhibit use of the late region polyadenylation site, resulting in increased stability of late region transcripts.
Similar articles
- Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes.
Hummel M, Hudson JB, Laimins LA. Hummel M, et al. J Virol. 1992 Oct;66(10):6070-80. doi: 10.1128/JVI.66.10.6070-6080.1992. J Virol. 1992. PMID: 1326657 Free PMC article. - Characterization of late gene transcripts expressed during vegetative replication of human papillomavirus type 31b.
Ozbun MA, Meyers C. Ozbun MA, et al. J Virol. 1997 Jul;71(7):5161-72. doi: 10.1128/JVI.71.7.5161-5172.1997. J Virol. 1997. PMID: 9188583 Free PMC article. - Temporal usage of multiple promoters during the life cycle of human papillomavirus type 31b.
Ozbun MA, Meyers C. Ozbun MA, et al. J Virol. 1998 Apr;72(4):2715-22. doi: 10.1128/JVI.72.4.2715-2722.1998. J Virol. 1998. PMID: 9525589 Free PMC article. - Keratinocyte Differentiation-Dependent Human Papillomavirus Gene Regulation.
Graham SV. Graham SV. Viruses. 2017 Aug 30;9(9):245. doi: 10.3390/v9090245. Viruses. 2017. PMID: 28867768 Free PMC article. Review. - HPV-16 RNA processing.
Schwartz S. Schwartz S. Front Biosci. 2008 May 1;13:5880-91. doi: 10.2741/3123. Front Biosci. 2008. PMID: 18508629 Review.
Cited by
- Epidermal growth factor receptor-dependent stimulation of differentiation by human papillomavirus type 16 E5.
Trammel J, Amusan O, Hultgren A, Raikhy G, Bodily JM. Trammel J, et al. Virology. 2024 Feb;590:109952. doi: 10.1016/j.virol.2023.109952. Epub 2023 Dec 12. Virology. 2024. PMID: 38103269 - Intra-Patient Genomic Variations of Human Papillomavirus Type 31 in Cervical Cancer and Precancer.
Kogure G, Tanaka K, Matsui T, Onuki M, Matsumoto K, Iwata T, Kukimoto I. Kogure G, et al. Viruses. 2023 Oct 17;15(10):2104. doi: 10.3390/v15102104. Viruses. 2023. PMID: 37896881 Free PMC article. - HPV16 and HPV18 Genome Structure, Expression, and Post-Transcriptional Regulation.
Yu L, Majerciak V, Zheng ZM. Yu L, et al. Int J Mol Sci. 2022 Apr 29;23(9):4943. doi: 10.3390/ijms23094943. Int J Mol Sci. 2022. PMID: 35563334 Free PMC article. Review. - Phthalocyanine and Its Formulations: A Promising Photosensitizer for Cervical Cancer Phototherapy.
Carobeli LR, Meirelles LEF, Damke GMZF, Damke E, Souza MVF, Mari NL, Mashiba KH, Shinobu-Mesquita CS, Souza RP, Silva VRSD, Gonçalves RS, Caetano W, Consolaro MEL. Carobeli LR, et al. Pharmaceutics. 2021 Dec 2;13(12):2057. doi: 10.3390/pharmaceutics13122057. Pharmaceutics. 2021. PMID: 34959339 Free PMC article. Review. - The chromatin insulator CTCF regulates HPV18 transcript splicing and differentiation-dependent late gene expression.
Ferguson J, Campos-León K, Pentland I, Stockton JD, Günther T, Beggs AD, Grundhoff A, Roberts S, Noyvert B, Parish JL. Ferguson J, et al. PLoS Pathog. 2021 Nov 4;17(11):e1010032. doi: 10.1371/journal.ppat.1010032. eCollection 2021 Nov. PLoS Pathog. 2021. PMID: 34735550 Free PMC article.
References
- Biochemistry. 1979 Nov 27;18(24):5294-9 - PubMed
- J Virol. 1989 Nov;63(11):4898-903 - PubMed
- Br J Dermatol. 1984 Jul;111 Suppl 27:219-22 - PubMed
- Oncogene. 1989 Dec;4(12):1529-32 - PubMed
- Trends Biochem Sci. 1989 Sep;14(9):373-7 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources