BINDING OF AN HIV REV PEPTIDE TO REV RESPONSIVE ELEMENT RNA INDUCES FORMATION OF PURINE-PURINE BASE-PAIRS

The Rev responsive element (RRE) is an RNA secondary structural elemen t within the env gene of HIV and is the binding site for the viral Rev protein. Formation of the Rev-RRE complex is involved in regulation o f splicing and transport of mRNA from the nucleus. To understand the s tructural basis for the specific recognition of RRE by Rev, we have st udied a model system for this interaction using NMR. We have obtained a specific 1:1 complex between an RNA derived from stem IIB of RRE, wh ich contains the highest affinity Rev binding site, and a modified Rev (34-50) peptide, which binds the RRE as an ct-helix [Tan, R., et al. ( 1993) Cell 73, 1031-1040]. Binding of the peptide was accompanied by a conformational change in the RNA, which resulted in the formation of additional base pairs not present in the free RNA. Two of these induce d base pairs are purine-purine pairs within the internal loop of RRE, which had been previously proposed on the basis of biochemical experim ents [Bartel, D. P., et al. (1991) Cell 67, 529-536]. The formation of non-Watson-Crick base pairs, interactions in the major groove, and pr otein-induced conformational changes may prove to be common characteri stics of RNA recognition of proteins.