Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting

Media type: E-Article

Title: Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting

Contributor: Tantale, Katjana; Garcia-Oliver, Encar; Robert, Marie-Cécile; L’Hostis, Adèle; Yang, Yueyuxiao; Tsanov, Nikolay; Topno, Rachel; Gostan, Thierry; Kozulic-Pirher, Alja; Basu-Shrivastava, Meenakshi; Mukherjee, Kamalika; Slaninova, Vera; Andrau, Jean-Christophe; Mueller, Florian; Basyuk, Eugenia; Radulescu, Ovidiu; Bertrand, Edouard

imprint: Springer Science and Business Media LLC, 2021

Language: English

DOI: 10.1038/s41467-021-24462-5

ISSN: 2041-1723

Origination:

Footnote:

Description: AbstractPromoter-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.

Access State: Open Access

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