The Exon Junction Complex core factor eIF4A3 is a key regulator of HPV16 gene expression.

Fiche publication


Date publication

mars 2021

Journal

Bioscience reports

Auteurs

Membres identifiés du Cancéropôle Est :
Pr AUBIN François, Dr BAGUET Aurélie, Pr GUITTAUT Michaël, Pr PRETET Jean-Luc


Tous les auteurs :
Meznad K, Paget-Bailly P, Jacquin E, Peigney A, Aubin F, Guittaut M, Mougin C, Prétet JL, Baguet A

Résumé

High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas. Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In this study, we investigated the implication of the DEAD-box helicase eIF4A3, an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 upregulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the upregulation of E7 at both RNA and protein levels. We therefore proposed that HPV16 transcripts might present different susceptibilities to NMD and that this pathway could play a key role in the levels of expression of these viral oncoproteins during the development of HPV-related cancers.

Mots clés

Cervical cancer, DDX48/eIF4A3, Exon Junction Complex, HPV

Référence

Biosci Rep. 2021 Mar 24;: