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Eukaryotic RNA Polymerases00:58

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RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Updated: Jan 16, 2026

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
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RNA Polymerase III Regulates HIV Replication and Latency.

Landon Thompson1, Imran Jamal1, Juthika Das1

  • 1Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA.

Viruses
|September 27, 2025
PubMed
Summary

Targeting RNA Polymerase III (RNAP III) can reactivate latent HIV reservoirs. Inhibiting RNAP III boosts HIV transcription, offering a novel strategy for HIV latency elimination.

Keywords:
HIV latencyHIV reactivationRNA Pol III

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Eliminating latent Human Immunodeficiency Virus (HIV) reservoirs is a major hurdle in achieving a cure.
  • Understanding the mechanisms regulating HIV latency is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of RNA Polymerase III (RNAP III) in regulating HIV latency and replication.
  • To explore RNAP III as a potential therapeutic target for reactivating latent HIV reservoirs.

Main Methods:

  • Pharmacological inhibition of RNAP III in cell lines (T and monocytic) and primary CD4 T cells.
  • Assessment of HIV transcription and latency reactivation using HIV-1 pseudotyped and HIV-1-Bal viruses.
  • Quantification of total HIV DNA to assess viral persistence.

Main Results:

  • Pharmacological inhibition of RNAP III strongly reactivated HIV latency in various cell models.
  • RNAP III inhibition significantly increased HIV transcription in cell lines and primary CD4 T cells up to 72 hours.
  • Total HIV DNA levels remained unchanged, indicating reactivation without increased viral production.

Conclusions:

  • RNA Polymerase III plays a previously unrecognized role in restricting HIV transcription.
  • Targeting RNAP III-driven mechanisms represents a novel strategy to reactivate latent HIV reservoirs.
  • RNAP III inhibition offers a potential pathway to enhance the efficacy of HIV eradication therapies.