HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells.
Elife
; 42015 Oct 21.
Article
en En
| MEDLINE
| ID: mdl-26488441
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
ARN Polimerasa II
/
VIH
/
Epigénesis Genética
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Productos del Gen tat del Virus de la Inmunodeficiencia Humana
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Interacciones Huésped-Patógeno
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos