Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting.
Language
EN
Article de revue
This item was published in
Nature Communications. 2021-07-23, vol. 12, n° 1, p. 4503
English 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 ...Read more >
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.Read less <
English Keywords
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