HIV Tat Controls RNA Polymerase II and the Epigenetic Landscape to Transcriptionally Reprogram Target Immune Cells

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HIV Tat Controls RNA Polymerase II and the Epigenetic Landscape to Transcriptionally Reprogram Target Immune Cells

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Title: HIV Tat Controls RNA Polymerase II and the Epigenetic Landscape to Transcriptionally Reprogram Target Immune Cells
Author(s):
Reeder, Jonathan E.;
Kwak, Youn-Tae;
McNamara, Ryan P.;
Forst, Christian V.;
D'Orso, Ivan
Item Type: article
Keywords: Show Keywords
Abstract: HIV encodes Tat, a small protein that facilitates viral transcription by binding an RNA structure (trans-activating RNA [TAR]) formed on nascent viral pre-messenger RNAs. 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 in target genes. We propose that a virus with a limited coding capacity has optimized its genome by evolving a small but 'multitasking' protein to simultaneously control viral and cellular transcription.
ISSN: 2050-084X
Link to Related Resource: http://dx.doi.org/10.7554/eLife.08955
Persistent Link: http://hdl.handle.net/10735.1/5637
Bibliographic Citation: Reeder, Jonathan E., Youn-Tae Kwak, Ryan P. McNamara, Christian V. Forst, et al. 2015. "HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells." eLife 4, doi:10.7554/eLife.08955
Terms of Use: CC BY 4.0 (Attribution)
©2015 The Authors. All Rights Reserved.
Sponsors: National Institute of Allergy and Infectious Diseases (R00AI083087, R56AI106514, and R01AI114362); The Welch Foundation (I-1782); NIH training grant T32 (2T32AI007520-16)

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CC BY 4.0 (Attribution) Except where otherwise noted, this item's license is described as CC BY 4.0 (Attribution)