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Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- SummaryPromoter-proximal polymerase pausing 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, and 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.
- Subjects :
- polymerase pausing
Transcriptional bursting
0303 health sciences
[SDV]Life Sciences [q-bio]
030302 biochemistry & molecular biology
RNA
Promoter
Biology
3. Good health
Cell biology
03 medical and health sciences
Bursting
single molecule imaging
Transcription (biology)
transcriptional noise
Gene expression
biology.protein
HIV-1 latency
bursting
Latency (engineering)
Polymerase
030304 developmental biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....3644279dedc69bf8626431e32c402cbb
- Full Text :
- https://doi.org/10.1101/2020.08.25.265413