Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element

Nucleic Acids Res. 2008 Apr;36(7):2353-65. doi: 10.1093/nar/gkn076. Epub 2008 Feb 24.


The interaction between human immunodeficiency virus type 1 (HIV-1) and RNA silencing pathways is complex and multifaceted. Essential for efficient viral transcription and supporting Tat-mediated transactivation of viral gene expression, the trans-activation responsive (TAR) element is a structured RNA located at the 5' end of all transcripts derived from HIV-1. Here, we report that this element is a source of microRNAs (miRNAs) in cultured HIV-1-infected cell lines and in HIV-1-infected human CD4+ T lymphocytes. Using primer extension and ribonuclease (RNase) protection assays, we delineated both strands of the TAR miRNA duplex deriving from a model HIV-1 transcript, namely miR-TAR-5p and miR-TAR-3p. In vitro RNase assays indicate that the lack of a free 3' extremity at the base of TAR may contribute to its low processing reactivity in vivo. Both miR-TAR-5p and miR-TAR-3p down-regulated TAR miRNA sensor activity in a process that required an integral miRNA-guided RNA silencing machinery. miR-TAR-3p exerted superior gene downregulatory effects, probably due to its preferential release from HIV-1 TAR RNA by the RNase III Dicer. Our study suggests that the TAR element of HIV-1 transcripts releases functionally competent miRNAs upon asymmetrical processing by Dicer, thereby providing novel insights into viral miRNA biogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Fragile X Mental Retardation Protein / metabolism
  • Gene Expression Regulation, Viral*
  • HIV Long Terminal Repeat*
  • HIV-1 / genetics*
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • RNA Processing, Post-Transcriptional*
  • RNA, Viral / chemistry
  • RNA, Viral / metabolism
  • Ribonuclease III / metabolism


  • MicroRNAs
  • RNA, Viral
  • Fragile X Mental Retardation Protein
  • Ribonuclease III