Specific regulation of mRNA splicing in vitro by a peptide from HIV-1 Rev

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The Rev protein of HIV-1 regulates the synthesis of partially spliced forms of cytoplasmic viral mRNA by binding to a cis-acting RNA sequence, the Rev response element (RRE). We have investigated the regulation of splicing in vitro and have shown that Rev specifically inhibits splicing of pre-mRNAs containing an RRE by 3- to 4-fold. A synthetic peptide of 17 amino acids containing the RNA-binding domain of Rev is highly functional and specifically inhibits splicing by up to 30-fold. Other peptides that bind to the RRE with high affinity, but with low specificity, do not specifically inhibit splicing. Six repeated monomeric binding sites for the peptide can substitute for the RRE, indicating that regulation by Rev requires interactions with multiple sites. The peptide acts at a step in the assembly of splicing complexes, suggesting that one of the functions of the basic region of Rev is to prevent formation of a functional spliceosome.
Original languageEnglish
JournalCell
Volume67
Issue1
Pages (from-to)169-178
Number of pages10
ISSN0092-8674
DOIs
Publication statusPublished - 1991

    Research areas

  • Amino Acid Sequence, Base Sequence, Binding Sites, Cell Nucleus, Cloning, Molecular, Gene Products, rev, Globins, HIV-1, HeLa Cells, Humans, Kinetics, Molecular Sequence Data, Oligodeoxyribonucleotides, Peptides, RNA Splicing, RNA, Messenger, Restriction Mapping, Transcription, Genetic, rev Gene Products, Human Immunodeficiency Virus

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