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

Jonathan E. Reeder, Youn Tae Kwak, Ryan P. McNamara, Christian V. Forst, Iván D’Orso

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article number08955
JournaleLife
Volume4
Issue numberOCTOBER2015
DOIs
StatePublished - Oct 21 2015

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RNA Polymerase II
Epigenomics
Transcription
Genes
HIV
RNA
Viruses
Nucleotide Motifs
Viral Proteins
Multitasking
Genome
Elongation
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells. / Reeder, Jonathan E.; Kwak, Youn Tae; McNamara, Ryan P.; Forst, Christian V.; D’Orso, Iván.

In: eLife, Vol. 4, No. OCTOBER2015, 08955, 21.10.2015.

Research output: Contribution to journalArticle

Reeder, Jonathan E. ; Kwak, Youn Tae ; McNamara, Ryan P. ; Forst, Christian V. ; D’Orso, Iván. / HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells. In: eLife. 2015 ; Vol. 4, No. OCTOBER2015.
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