HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells
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 mec...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/08955 |
| _version_ | 1811200316168732672 |
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| author | Jonathan E Reeder Youn-Tae Kwak Ryan P McNamara Christian V Forst Iván D'Orso |
| author_facet | Jonathan E Reeder Youn-Tae Kwak Ryan P McNamara Christian V Forst Iván D'Orso |
| author_sort | Jonathan E Reeder |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:02:42Z |
| format | Article |
| id | doaj.art-befdd0611f694c9ea4095c29742598ed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:02:42Z |
| publishDate | 2015-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-befdd0611f694c9ea4095c29742598ed2022-12-22T03:52:38ZengeLife Sciences Publications LtdeLife2050-084X2015-10-01410.7554/eLife.08955HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cellsJonathan E Reeder0Youn-Tae Kwak1Ryan P McNamara2Christian V Forst3Iván D'Orso4https://orcid.org/0000-0002-1409-2351Department of Biological Sciences, University of Texas at Dallas, Richardson, United States; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, United StatesHIV 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.https://elifesciences.org/articles/08955transcription factorchromatinRNA polymerase IIepigenetictranscription |
| spellingShingle | Jonathan E Reeder Youn-Tae Kwak Ryan P McNamara Christian V Forst Iván D'Orso HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells eLife transcription factor chromatin RNA polymerase II epigenetic transcription |
| title | HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells |
| title_full | HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells |
| title_fullStr | HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells |
| title_full_unstemmed | HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells |
| title_short | HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells |
| title_sort | hiv tat controls rna polymerase ii and the epigenetic landscape to transcriptionally reprogram target immune cells |
| topic | transcription factor chromatin RNA polymerase II epigenetic transcription |
| url | https://elifesciences.org/articles/08955 |
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