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

Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1882-7. doi: 10.1073/pnas.042693399.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Binding Sites
  • Dimerization
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation* / drug effects
  • Genes, Reporter
  • Kinetics
  • Ligands
  • Models, Chemical
  • Nucleic Acid Conformation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Biosynthesis
  • RNA / metabolism*
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism
  • Streptavidin / metabolism
  • Transcription, Genetic

Substances

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Ligands
  • RNA, Messenger
  • Ribosomal Proteins
  • ribosomal protein S80
  • RNA
  • Streptavidin