Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting

Katjana Tantale, Encar Garcia-Oliver, Marie-Cécile Robert, Adèle L’Hostis, Yueyuxiao Yang, Nikolay Tsanov, Rachel Topno, Thierry Gostan, Alja Kozulic-Pirher, Meenakshi Basu-Shrivastava, Kamalika Mukherjee, Vera Slaninova, Jean-Christophe Andrau, Florian Mueller, Eugenia Basyuk (), Ovidiu Radulescu () and Edouard Bertrand ()
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Katjana Tantale: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Encar Garcia-Oliver: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Marie-Cécile Robert: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Adèle L’Hostis: LPHI, UMR CNRS 5235, University of Montpellier
Yueyuxiao Yang: LPHI, UMR CNRS 5235, University of Montpellier
Nikolay Tsanov: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Rachel Topno: Equipe labélisée Ligue Nationale Contre le Cancer, University of Montpellier, CNRS
Thierry Gostan: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Alja Kozulic-Pirher: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Meenakshi Basu-Shrivastava: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Kamalika Mukherjee: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Vera Slaninova: Equipe labélisée Ligue Nationale Contre le Cancer, University of Montpellier, CNRS
Jean-Christophe Andrau: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Florian Mueller: Unité Imagerie et Modélisation, Institut Pasteur and CNRS UMR 3691
Eugenia Basyuk: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS
Ovidiu Radulescu: LPHI, UMR CNRS 5235, University of Montpellier
Edouard Bertrand: Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24462-5

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DOI: 10.1038/s41467-021-24462-5

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