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Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism
High-risk Human Papillomavirus infections are responsible for anogenital and oropharyngeal cancers. Alternative splicing is an important mechanism controlling HPV16 gene expression. Modulation in the splice pattern leads to polycistronic HPV16 early transcripts encoding a full length E6 oncoprotein...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459911/ https://www.ncbi.nlm.nih.gov/pubmed/30976051 http://dx.doi.org/10.1038/s41598-019-42393-6 |
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author | Paget-Bailly, Philippe Meznad, Koceila Bruyère, Diane Perrard, Jérôme Herfs, Michael Jung, Alain C. Mougin, Christiane Prétet, Jean-Luc Baguet, Aurélie |
author_facet | Paget-Bailly, Philippe Meznad, Koceila Bruyère, Diane Perrard, Jérôme Herfs, Michael Jung, Alain C. Mougin, Christiane Prétet, Jean-Luc Baguet, Aurélie |
author_sort | Paget-Bailly, Philippe |
collection | PubMed |
description | High-risk Human Papillomavirus infections are responsible for anogenital and oropharyngeal cancers. Alternative splicing is an important mechanism controlling HPV16 gene expression. Modulation in the splice pattern leads to polycistronic HPV16 early transcripts encoding a full length E6 oncoprotein or truncated E6 proteins, commonly named E6*. Spliced E6*I transcripts are the most abundant RNAs produced in HPV-related cancers. To date, the biological function of the E6*I isoform remains controversial. In this study, we identified, by RNA sequencing, cellular targets deregulated by E6*I, among which genes related to ROS metabolism. Concomitantly, E6*I-overexpressing cells display high levels of ROS. However, co-overexpression of both E6 and E6*I has no effect on ROS production. In HPV16-infected cells expressing different E6/E6*I levels, we show that the newly identified targets CCL2 and RAC2 are increased by E6*I but decreased by E6 expression, suggesting that E6 abrogates the effect of E6*I. Taken together, these data support the idea that E6*I acts independently of E6 to increase ROS production and that E6 has the ability to counteract the effects of E6*I. This asks the question of how E6*I can be considered separately of E6 in the natural history of HPV16 infection. |
format | Online Article Text |
id | pubmed-6459911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64599112019-04-16 Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism Paget-Bailly, Philippe Meznad, Koceila Bruyère, Diane Perrard, Jérôme Herfs, Michael Jung, Alain C. Mougin, Christiane Prétet, Jean-Luc Baguet, Aurélie Sci Rep Article High-risk Human Papillomavirus infections are responsible for anogenital and oropharyngeal cancers. Alternative splicing is an important mechanism controlling HPV16 gene expression. Modulation in the splice pattern leads to polycistronic HPV16 early transcripts encoding a full length E6 oncoprotein or truncated E6 proteins, commonly named E6*. Spliced E6*I transcripts are the most abundant RNAs produced in HPV-related cancers. To date, the biological function of the E6*I isoform remains controversial. In this study, we identified, by RNA sequencing, cellular targets deregulated by E6*I, among which genes related to ROS metabolism. Concomitantly, E6*I-overexpressing cells display high levels of ROS. However, co-overexpression of both E6 and E6*I has no effect on ROS production. In HPV16-infected cells expressing different E6/E6*I levels, we show that the newly identified targets CCL2 and RAC2 are increased by E6*I but decreased by E6 expression, suggesting that E6 abrogates the effect of E6*I. Taken together, these data support the idea that E6*I acts independently of E6 to increase ROS production and that E6 has the ability to counteract the effects of E6*I. This asks the question of how E6*I can be considered separately of E6 in the natural history of HPV16 infection. Nature Publishing Group UK 2019-04-11 /pmc/articles/PMC6459911/ /pubmed/30976051 http://dx.doi.org/10.1038/s41598-019-42393-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Paget-Bailly, Philippe Meznad, Koceila Bruyère, Diane Perrard, Jérôme Herfs, Michael Jung, Alain C. Mougin, Christiane Prétet, Jean-Luc Baguet, Aurélie Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism |
title | Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism |
title_full | Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism |
title_fullStr | Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism |
title_full_unstemmed | Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism |
title_short | Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism |
title_sort | comparative rna sequencing reveals that hpv16 e6 abrogates the effect of e6*i on ros metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459911/ https://www.ncbi.nlm.nih.gov/pubmed/30976051 http://dx.doi.org/10.1038/s41598-019-42393-6 |
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