An HIV-Encoded Antisense Long Noncoding RNA Epigenetically Regulates Viral Transcription

• Published in: Molecular therapy Vol. 22; no. 6; pp. 1164 - 1175
• Main Authors: Saayman, Sheena, Ackley, Amanda, Turner, Anne-Marie W, Famiglietti, Marylinda, Bosque, Alberto, Clemson, Matthew, Planelles, Vicente, Morris, Kevin V
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2014; Elsevier Limited; Nature Publishing Group
• Subjects: Azacitidine - pharmacology; Cloning; Epigenesis, Genetic; Epigenetics; Gene expression; Gene Expression Regulation, Viral - drug effects; Genomes; HEK293 Cells; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus; Humans; Hydroxamic Acids - pharmacology; Infections; Jurkat Cells; Original; Promoter Regions, Genetic; Proteins; RNA, Antisense - genetics; RNA, Long Noncoding - genetics; RNA, Messenger - genetics; RNA, Viral - genetics; Viral infections; La Jolla California; United States > US; California
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2014.29

The abundance of long noncoding RNAs (lncRNAs) and their wide range of functional roles in human cells are fast becoming realized. Importantly, lncRNAs have been identified as epigenetic modulators and consequently play a pivotal role in the regulation of gene expression. A human immunodeficiency virus-encoded antisense RNA transcript has recently been reported and we sought to characterize this RNA and determine its potential role in viral transcription regulation. The intrinsic properties of this human immunodeficiency virus-expressed lncRNA were characterized and the data presented here suggest that it functions as an epigenetic brake to modulate viral transcription. Suppression of this long antisense transcript with small single-stranded antisense RNAs resulted in the activation of viral gene expression. This lncRNA was found to localize to the 5′ long-term repeats (LTR) and to usurp components of endogenous cellular pathways that are involved in lncRNA directed epigenetic gene silencing. Collectively, we find that this viral expressed antisense lncRNA is involved in modulating human immunodeficiency virus gene expression and that this regulatory effect is due to an alteration in the epigenetic landscape at the viral promoter.