title: An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription.
abstract: 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.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Sheena
authors.initials: S
authors.lastname: Saayman
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ackley
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Anne-Marie W
authors.initials: AW
authors.lastname: Turner
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Marylinda
authors.initials: M
authors.lastname: Famiglietti
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosque
authors.affiliation: School of Biotechnology and Biomedical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Clemson
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Planelles
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA; School of Biotechnology and Biomedical Sciences, University of New South Wales, Sydney, Australia. Electronic address: kmorris@scripps.edu.
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Morris
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D044127:Epigenesis, Genetic; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*
chemical_list: D006877:Hydroxamic Acids; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012367:RNA, Viral; C012589:trichostatin A; D001374:Azacitidine