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Article Dans Une Revue Nature Communications Année : 2021

Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting

Rachel Topno
Thierry Gostan
  • Fonction : Auteur
Alja Kozulic-Pirher
  • Fonction : Auteur
Meenakshi Basu-Shrivastava
  • Fonction : Auteur
Kamalika Mukherjee
Vera Slaninova
Jean-Christophe Andrau
Florian Mueller
Eugenia Basyuk
Ovidiu Radulescu

Résumé

Promoter-proximal pausing of RNA polymerase II is a key process regulating gene expression. In latent HIV-1 cells, it prevents viral transcription and is essential for latency maintenance, while in acutely infected cells the viral factor Tat releases paused polymerase to induce viral expression. Pausing is fundamental for HIV-1, but how it contributes to bursting and stochastic viral reactivation is unclear. Here, we performed single molecule imaging of HIV-1 transcription. We developed a quantitative analysis method that manages multiple time scales from seconds to days and that rapidly fits many models of promoter dynamics. We found that RNA polymerases enter a long-lived pause at latent HIV-1 promoters (>20 minutes), thereby effectively limiting viral transcription. Surprisingly and in contrast to current models, pausing appears stochastic and not obligatory, with only a small fraction of the polymerases undergoing long-lived pausing in absence of Tat. One consequence of stochastic pausing is that HIV-1 transcription occurs in bursts in latent cells, thereby facilitating latency exit and providing a rationale for the stochasticity of viral rebounds.
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Dates et versions

hal-03382893 , version 1 (18-10-2021)

Identifiants

Citer

Katjana Tantale, Encar Garcia-Oliver, Marie-Cécile Robert, Adèle L’hostis, Yueyuxiao Yang, et al.. Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting. Nature Communications, 2021, 12 (1), pp.4503. ⟨10.1038/s41467-021-24462-5⟩. ⟨hal-03382893⟩
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