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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...

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Autores principales: Paget-Bailly, Philippe, Meznad, Koceila, Bruyère, Diane, Perrard, Jérôme, Herfs, Michael, Jung, Alain C., Mougin, Christiane, Prétet, Jean-Luc, Baguet, Aurélie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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