title: HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression.
abstract: BACKGROUND
  RNA interference is a gene regulatory mechanism that employs small RNA molecules such as microRNA. Previous work has shown that HIV-1 produces TAR viral microRNA. Here we describe the effects of the HIV-1 TAR derived microRNA on cellular gene expression.
  
  
  RESULTS
  Using a variation of standard techniques we have cloned and sequenced both the 5' and 3' arms of the TAR miRNA. We show that expression of the TAR microRNA protects infected cells from apoptosis and acts by down-regulating cellular genes involved in apoptosis. Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis. Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.
  
  
  CONCLUSIONS
  The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.
authors.affiliation: The Department of Microbiology, Immunology and Tropical Medicine program, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA. bcmzak@gwumc.edu
authors.forename: Zachary
authors.initials: Z
authors.lastname: Klase
authors.forename: Rafael
authors.initials: R
authors.lastname: Winograd
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Davis
authors.forename: Lawrence
authors.initials: L
authors.lastname: Carpio
authors.forename: Richard
authors.initials: R
authors.lastname: Hildreth
authors.forename: Mohammad
authors.initials: M
authors.lastname: Heydarian
authors.forename: Sidney
authors.initials: S
authors.lastname: Fu
authors.forename: Timothy
authors.initials: T
authors.lastname: McCaffrey
authors.forename: Eti
authors.initials: E
authors.lastname: Meiri
authors.forename: Mila
authors.initials: M
authors.lastname: Ayash-Rashkovsky
authors.forename: Shlomit
authors.initials: S
authors.lastname: Gilad
authors.forename: Zwi
authors.initials: Z
authors.lastname: Bentwich
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000502:physiology*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D016415:Sequence Alignment; D020298:U937 Cells
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C071447:ERCC1 protein, human; D004720:Endonucleases; D043244:Ribonuclease III; D053148:Caspase 3