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

doi:10.1038/s41467-021-24462-5

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Article de revue

Ce document a été publié dans

Nature Communications. 2021-07-23, vol. 12, n° 1, p. 4503

Résumé en anglais

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.< Réduire

Mots clés en anglais

Algorithms

DNA-Directed RNA Polymerases

Gene Expression Regulation

Viral

HIV Infections

HIV-1

HeLa Cells

Humans

Models

Genetic

Promoter Regions

Genetic

Stochastic Processes

Time Factors

Virus Activation

Virus Latency

tat Gene Products

Human Immunodeficiency Virus

URI

https://oskar-bordeaux.fr/handle/20.500.12278/203065

DOI

http://dx.doi.org/10.1038/s41467-021-24462-5

Unités de recherche

MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234

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Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting.

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Résumé en anglais

Mots clés en anglais

URI

DOI

Unités de recherche