Selection of RNA-binding peptides in vivo

Abstract

MANY principles of sequence-specific DNA recognition have been established over the past decade, largely from structural studies of protein–DNA and drug–DNA complexes. On the basis of these principles, it has been possible to design or select variants of known structural motifs, including zinc-fingers1–3 and minor groove-binding drugs4, that bind desired sequences. Here we describe a strategy, based on transcriptional termination in bacteria, to identify specific RNA-binding peptides using the arginine-rich RNA-binding motif5 as a framework. Peptides were isolated from two combinatorial libraries that bind tightly and specifically to the Rev response element of HIV. It appears that α-helical peptides resembling Rev were selected from one library whereas new peptides that probably do not form helices were selected from the other, suggesting that the arginine-rich motif may be a particularly versatile framework for recognizing RNA structures.