Forced engagement of a RNA/protein complex by a chemical inducer of dimerization to modulate gene expression.

Abstract

A general strategy is described for forcing the engagement of an RNA/protein complex by using small-molecule ligands. A bivalent molecule was created by linking a protein-binding ligand to an RNA-binding ligand. On presentation of the chemical inducer of dimerization to the RNA by the protein, cooperative binding ensued, resulting in higher-affinity complexes. When the chemical inducer of dimerization was used to target the protein to an mRNA template, the resulting RNA/protein complex was sufficiently stable to inhibit mRNA translation. This approach provides a logic to modulate gene expression by using small-molecule ligands to recruit protein surfaces to mRNAs.