HIV Rev-dependent binding of SF2/ASF to the Rev response element: possible role in Rev-mediated inhibition of HIV RNA splicing

Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):973-8. doi: 10.1073/pnas.94.3.973.


Production of the structural and enzymatic proteins of type 1 human immunodeficiency virus (HIV-1) is controlled by the rev regulatory gene product. The 116-amino acid Rev protein acts by binding to the Rev response element (RRE), a complex RNA stem-loop structure located within the env gene of HIV. Rev exerts a series of posttranscriptional effects, including the inhibition of viral RNA splicing, the activation of nuclear export of incompletely spliced viral RNAs, and the enhancement of translation of RRE-containing RNAs. Our studies now demonstrate that at least one member of the SR family of splicing factors, SF2/ASF, specifically binds to a subregion of the RRE in vitro in a Rev-dependent manner. Furthermore, expression of high levels of SF2/ASF inhibits Rev function and impairs HIV replication in vivo. Both the in vitro binding of SF2/ASF to the Rev/RRE complex and the in vivo inhibition of Rev action by SF2/ASF are abrogated by mutation of the N-terminal RNA recognition motif but are not affected by mutation of the C-terminal arginine-serine-rich domain. These findings suggest that Rev inhibition of HIV splicing likely involves recruitment of the essential splicing factor SF2/ASF to the Rev/RRE complex. However, these inhibitory effects of Rev on viral RNA splicing are apparently overcome by augmenting the intracellular levels of SF2/ASF expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • Cell Extracts
  • Cell Line
  • Cell Nucleus
  • Fibroblasts
  • Gene Products, rev / genetics
  • Gene Products, rev / physiology*
  • HIV-1 / genetics*
  • Haplorhini
  • HeLa Cells
  • Human T-lymphotropic virus 1 / genetics
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA Splicing / physiology*
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins
  • Serine-Arginine Splicing Factors
  • Virus Replication
  • rev Gene Products, Human Immunodeficiency Virus


  • Cell Extracts
  • Gene Products, rev
  • Nuclear Proteins
  • RNA, Viral
  • RNA-Binding Proteins
  • rev Gene Products, Human Immunodeficiency Virus
  • Serine-Arginine Splicing Factors