Forced engagement of a RNA/protein complex by a chemical inducer of dimerization to modulate gene expression.
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.
Harvey
Isabelle
I
Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6.
Garneau
Philippe
P
Pelletier
Jerry
J
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D001665:Binding Sites; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D019809:Streptavidin / Q000378:metabolism; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D008024:Ligands; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C039913:ribosomal protein S80; D012313:RNA; D019809:Streptavidin