Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Retrovirology Année : 2009

Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein.

Nicolas Charnay
  • Fonction : Auteur
  • PersonId : 918478
Roland Ivanyi-Nagy
  • Fonction : Auteur
  • PersonId : 918479
Ricardo Soto-Rifo
  • Fonction : Auteur
  • PersonId : 918480
TEV
Théophile Ohlmann
  • Fonction : Auteur
  • PersonId : 918481
TEV
Marcelo López-Lastra
  • Fonction : Auteur
  • PersonId : 918482
Jean-Luc Darlix
Connectez-vous pour contacter l'auteur

Résumé

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) Tat protein is a major viral transactivator required for HIV-1 replication. In the nucleus Tat greatly stimulates the synthesis of full-length transcripts from the HIV-1 promoter by causing efficient transcriptional elongation. Tat induces elongation by directly interacting with the bulge of the transactivation response (TAR) RNA, a hairpin-loop located at the 5'-end of all nascent viral transcripts, and by recruiting cellular transcriptional co-activators. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. Thus, Tat plays a central role in the regulation of HIV-1 gene expression both at the level of mRNA and protein synthesis. The requirement of Tat in these processes poses an essential question on how sufficient amounts of Tat can be made early on in HIV-1 infected cells to sustain its own synthesis. To address this issue we studied translation of the Tat mRNA in vitro and in human cells using recombinant monocistronic and dicistronic RNAs containing the 5' untranslated region (5'-UTR) of Tat RNA. RESULTS: This study shows that the Tat mRNA can be efficiently translated both in vitro and in cells. Furthermore, our data suggest that translation initiation from the Tat mRNA probably occurs by a internal ribosome entry site (IRES) mechanism. Finally, we show that Tat protein can strongly stimulate translation from its cognate mRNA in a TAR dependent fashion. CONCLUSION: These results indicate that Tat mRNA translation is efficient and benefits from a feedback stimulation by the Tat protein. This translational control mechanism would ensure that minute amounts of Tat mRNA are sufficient to generate enough Tat protein required to stimulate HIV-1 replication.
Fichier principal
Vignette du fichier
1742-4690-6-74.pdf (842.64 Ko) Télécharger le fichier
1742-4690-6-74-S1.PPT (37.5 Ko) Télécharger le fichier
1742-4690-6-74-S2.PPT (111.5 Ko) Télécharger le fichier
1742-4690-6-74-S3.PPT (85 Ko) Télécharger le fichier
1742-4690-6-74.xml (141.23 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Loading...

Dates et versions

inserm-00663616 , version 1 (27-01-2012)

Identifiants

Citer

Nicolas Charnay, Roland Ivanyi-Nagy, Ricardo Soto-Rifo, Théophile Ohlmann, Marcelo López-Lastra, et al.. Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein.. Retrovirology, 2009, 6 (1), pp.74. ⟨10.1186/1742-4690-6-74⟩. ⟨inserm-00663616⟩
226 Consultations
278 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More