SELECTION OF RNA-BINDING PEPTIDES IN-VIVO

Many principles of sequence-specific DNA recognition have been establi shed over the past decade, largely from structural studies of protein- DNA and drug-DNA complexes. On the basis of these principles, it has b een possible to design or select variants of known structural motifs, including zinc-fingers(1-3) and minor groove-binding drugs', that bind desired sequences. Here we describe a strategy, based on transcriptio nal termination in bacteria, to identify specific RNA-binding peptides using the arginine-rich RNA-binding motifs as a framework. Peptides w ere isolated from two combinatorial libraries that bind tightly and sp ecifically to the Rev response element of HIV. It appears that a-helic al peptides resembling Rev were selected from one library whereas new peptides that probably do not form helices were selected from the othe r, suggesting that the arginine-rich motif may be a particularly versa tile framework for recognizing RNA structures.