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

Douglas M. Powell*, M. Catherine Amaral, Jane Y. Wu, Tom Maniatis, Warner C. Greene

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Production of the structural and enzymatic proteins of type I 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.

Original languageEnglish (US)
Pages (from-to)973-978
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number3
DOIs
StatePublished - Feb 4 1997

ASJC Scopus subject areas

  • General

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