ArticleScience advances2023
Enhancing HIV-1 latency reversal through regulating the elongating RNA Pol II pause-release by a small-molecule disruptor of PAF1C.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- High-resolution Sequencing Reveals that the Paf1 Complex May be a Conserved Transcription Elongation Factor for Eukaryotic RNA Polymerase I.Journal of molecular biology · 2025Article
- MYC: The Guardian of Its Own Chaos.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub.Nature communications · 2025Article
- The HIV-1 Transcriptional Program: From Initiation to Elongation Control.Journal of molecular biology · 2025Review
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.PLoS pathogens · 2024Article
- Aberrant RNA polymerase initiation and processivity on the genome of a herpes simplex virus 1 mutant lacking ICP27.Journal of virology · 2024Article
- Transcriptional elongation control of hypoxic response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.bioRxiv : the preprint server for biology · 2024Article
- PAF1c links S-phase progression to immune evasion and MYC function in pancreatic carcinoma.Nature communications · 2024Article
- Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure.Viruses · 2023Review
- Transcriptional elongation control in developmental gene expression, aging, and disease.Molecular cell · 2023Review
- PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex.Nature communications · 2023Article
- Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The polymerase-associated factor 1 complex (PAF1C) is a key, post-initiation transcriptional regulator of both promoter-proximal pausing and productive elongation catalyzed by RNA Pol II and is also involved in transcriptional repression of viral gene expression during human immunodeficiency virus-1 (HIV-1) latency. Using a molecular docking-based compound screen in silico and global sequencing-based candidate evaluation in vivo, we identified a first-in-class, small-molecule inhibitor of PAF1C (iPAF1C) that disrupts PAF1 chromatin occupancy and induces global release of promoter-proximal paused RNA Pol II into gene bodies. Transcriptomic analysis revealed that iPAF1C treatment mimics acute PAF1 subunit depletion and impairs RNA Pol II pausing at heat shock-down-regulated genes. Furthermore, iPAF1C enhances the activity of diverse HIV-1 latency reversal agents both in cell line latency models and in primary cells from persons living with HIV-1. In sum, this study demonstrates that efficient disruption of PAF1C by a first-in-class, small-molecule inhibitor may have therapeutic potential for improving current HIV-1 latency reversal strategies.
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Registered trials
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