HIV Tat controls RNA Polymerase II and the epigenetic landscapeto transcriptionally reprogram target immune cells

  1. Jonathan E Reeder
  2. Youn-Tae Kwak
  3. Ryan P McNamara
  4. Christian V Forst
  5. Iván D'Orso  Is a corresponding author
  1. University of Texas at Dallas, United States
  2. University of Texas Southwestern Medical Center, United States
  3. Icahn School of Medicine at Mount Sinai, United States

Abstract

HIV encodes Tat, a small protein that facilitates viral transcription by binding an RNA structure (TAR) formed on nascent viral pre-mRNAs. Besides this well characterized mechanism, Tat appears to modulate cellular transcription, but the target genes and molecular mechanisms remain poorly understood. We report here that Tat uses unexpected regulatory mechanisms to reprogram target immune cells to promote viral replication and rewire pathways beneficial for the virus. Tat functions through master transcriptional regulators bound at promoters and enhancers, rather than through cellular "TAR-like" motifs, to both activate and repress gene sets sharing common functional annotations. Despite the complexity of transcriptional regulatory mechanisms in the cell, Tat precisely controls RNA Polymerase II recruitment and pause release to fine-tune the initiation and elongation steps. We propose that a virus with a limited coding capacity optimized its genome by evolving a small but "multitasking" protein to simultaneously control viral and cellular transcription.-

Article and author information

Author details

  1. Jonathan E Reeder

    Biology, University of Texas at Dallas, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Youn-Tae Kwak

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ryan P McNamara

    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christian V Forst

    Department of Genetics and Genomc Sciences, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Iván D'Orso

    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    Ivan.Dorso@UTSouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Michael R Green, Howard Hughes Medical Institute, University of Massachusetts Medical School, United States

Version history

  1. Received: May 27, 2015
  2. Accepted: October 20, 2015
  3. Accepted Manuscript published: October 21, 2015 (version 1)
  4. Accepted Manuscript updated: October 22, 2015 (version 2)
  5. Version of Record published: January 19, 2016 (version 3)

Copyright

© 2015, Reeder et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,005
    Page views
  • 714
    Downloads
  • 35
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jonathan E Reeder
  2. Youn-Tae Kwak
  3. Ryan P McNamara
  4. Christian V Forst
  5. Iván D'Orso
(2015)
HIV Tat controls RNA Polymerase II and the epigenetic landscapeto transcriptionally reprogram target immune cells
eLife 4:e08955.
https://doi.org/10.7554/eLife.08955

Share this article

https://doi.org/10.7554/eLife.08955

Further reading

    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology
    Arthur L Schneider, Rita Martins-Silva ... Nuno L Barbosa-Morais
    Tools and Resources

    We herein introduce voyAGEr, an online graphical interface to explore age-related gene expression alterations in 49 human tissues. voyAGEr offers a visualisation and statistical toolkit for the finding and functional exploration of sex- and tissue-specific transcriptomic changes with age. In its conception, we developed a novel bioinformatics pipeline leveraging RNA sequencing data, from the GTEx project, encompassing more than 900 individuals. voyAGEr reveals transcriptomic signatures of the known asynchronous ageing between tissues, allowing the observation of tissue-specific age periods of major transcriptional changes, associated with alterations in different biological pathways, cellular composition, and disease conditions. Notably, voyAGEr was created to assist researchers with no expertise in bioinformatics, providing a supportive framework for elaborating, testing and refining their hypotheses on the molecular nature of human ageing and its association with pathologies, thereby also aiding in the discovery of novel therapeutic targets. voyAGEr is freely available at https://compbio.imm.medicina.ulisboa.pt/app/voyAGEr.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Erandi Velazquez-Miranda, Ming He
    Insight

    Endothelial cell subpopulations are characterized by unique gene expression profiles, epigenetic landscapes and functional properties.