Tat-dependent production of an HIV-1 TAR-encoded miRNA-like small RNA

Nucleic Acids Res. 2016 May 19;44(9):4340-53. doi: 10.1093/nar/gkw167. Epub 2016 Mar 16.


Evidence is accumulating that retroviruses can produce microRNAs (miRNAs). To prevent cleavage of their RNA genome, retroviruses have to use an alternative RNA source as miRNA precursor. The transacting responsive (TAR) hairpin structure in HIV-1 RNA has been suggested as source for miRNAs, but how these small RNAs are produced without impeding virus replication remained unclear. We used deep sequencing analysis of AGO2-bound HIV-1 RNAs to demonstrate that the 3' side of the TAR hairpin is processed into a miRNA-like small RNA. This ∼21 nt RNA product is able to repress the expression of mRNAs bearing a complementary target sequence. Analysis of the small RNAs produced by wild-type and mutant HIV-1 variants revealed that non-processive transcription from the HIV-1 LTR promoter results in the production of short TAR RNAs that serve as precursor. These TAR RNAs are cleaved by Dicer and processing is stimulated by the viral Tat protein. This biogenesis pathway differs from the canonical miRNA pathway and allows HIV-1 to produce the TAR-encoded miRNA-like molecule without cleavage of the RNA genome.

MeSH terms

  • Argonaute Proteins / metabolism
  • Base Sequence
  • Gene Expression Regulation, Viral
  • HCT116 Cells
  • HEK293 Cells
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / physiology*
  • Humans
  • Inverted Repeat Sequences
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Promoter Regions, Genetic
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • Transcription, Genetic
  • Virus Replication
  • tat Gene Products, Human Immunodeficiency Virus / physiology*


  • AGO2 protein, human
  • Argonaute Proteins
  • MicroRNAs
  • RNA, Viral
  • tat Gene Products, Human Immunodeficiency Virus