Comparative RNA sequencing reveals that HPV16 E6 abrogates the effect of E6*I on ROS metabolism.
Fiche publication
Date publication
avril 2019
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGUET Aurélie, Dr JUNG Alain, Pr PRETET Jean-Luc
Tous les auteurs :
Paget-Bailly P, Meznad K, Bruyère D, Perrard J, Herfs M, Jung AC, Mougin C, Prétet JL, Baguet A
Lien Pubmed
Résumé
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.
Référence
Sci Rep. 2019 Apr 11;9(1):5938