Tat IRES modulator of tat mRNA (TIM-TAM): a conserved RNA structure that controls Tat expression and acts as a switch for HIV productive and latent infection.
Fiche publication
Date publication
décembre 2019
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRANLANT Christiane
Tous les auteurs :
Khoury G, Mackenzie C, Ayadi L, Lewin SR, Branlant C, Purcell DFJ
Lien Pubmed
Résumé
Tat protein is essential to fully activate HIV transcription and processing of viral mRNA, and therefore determines virus expression in productive replication and the establishment and maintenance of latent infection. Here, we used thermodynamic and structure analyses to define a highly conserved sequence-structure in tat mRNA that functions as Tat IRES modulator of tat mRNA (TIM-TAM). By impeding cap-dependent ribosome progression during authentic spliced tat mRNA translation, TIM-TAM stable structure impacts on timing and level of Tat protein hence controlling HIV production and infectivity along with promoting latency. TIM-TAM also adopts a conformation that mediates Tat internal ribosome entry site (IRES)-dependent translation during the early phases of infection before provirus integration. Our results document the critical role of TIM-TAM in Tat expression to facilitate virus reactivation from latency, with implications for HIV treatment and drug development.
Référence
Nucleic Acids Res.. 2019 Dec 25;: