An RNA-binding peptide from bovine immunodeficiency virus Tat protein recognizes an unusual RNA structure.

Abstract

The human immunodeficiency virus (HIV) Tat protein binds specifically to an RNA hairpin, TAR, located at the 5' end of its mRNA. Tat uses a single arginine residue within a short region of basic amino acids to recognize a bulge region in TAR. Here we show that a 17 amino acid arginine-rich peptide from the bovine immunodeficiency virus (BIV) Tat protein also binds to an RNA hairpin at the 5' end of its mRNA (BIV TAR), but recognizes different structural features of the RNA. Mutagenesis, RNase mapping, and chemical interference experiments indicate that bulge and stem regions of BIV TAR are recognized simultaneously by the BIV peptide and that the RNA adopts an unusual structure. BIV Tat binds to its TAR site with high affinity and specificity and, unlike HIV Tat, does not appear to use cellular proteins to stabilize RNA binding in vivo. Thus, two related viral activators have evolved rather distinct ways to recognize their RNA targets.