And The French Ministry Of Research And Technologythe Exon Junction Complex Core Factor Eif4a3 Is A Key Regulator Of Hpv16 Gene Expression

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 (HNSCCs). Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In the present study, we investigated the implication of the DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 up-regulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the up-regulation 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.Human papillomaviruses (HPVs) are small non-enveloped viruses with circular double-stranded DNA genomes. More than 200 types of HPVs infect humans [1] and are classified according to their carcinogenic potential. High-risk HPV types (hrHPVs) (including HPV16 and HPV18) are the etiological agents of cervical and anal carcinomas and frequently found in head and neck squamous cell carcinomas (HNSCCs), and low-risk HPV types (lrHPVs) (including HPV6 and HPV11) are associated with benign le