Manipulation of the peptide-binding specificity of an RNA in a rational manner by combinations of specificity-altering mutations

Abstract

In this study, the potential to manipulate the peptide-binding specificity of an RNA in a rational manner was investigated. First, variants of the Rev-response element (RRE) RNA with different specificities towards the natural binding partner, Rev, and two RRE-binding aptamers, the RSG-1.2 and K1 peptides, were identified. Next, hybrid RRE mutants with combinations of two sets of specificity-altering substitutions were tested for peptide-binding specificity. It was shown that, in most cases, the results of the combination of individual mutations were of an additive nature, therefore providing a way to manipulate the peptide-binding specificity of an RNA in a predictable manner.