Title: Direct and specific chemical control of eukaryotic translation with a synthetic RNA-protein interaction.
Authors: Goldfless, Stephen J; Belmont, Brian J; de Paz, Alexandra M; Liu, Jessica F; Niles, Jacquin C
Published In Nucleic Acids Res, (2012 May)
Abstract: Sequence-specific RNA-protein interactions, though commonly used in biological systems to regulate translation, are challenging to selectively modulate. Here, we demonstrate the use of a chemically-inducible RNA-protein interaction to regulate eukaryotic translation. By genetically encoding Tet Repressor protein (TetR)-binding RNA elements into the 5'-untranslated region (5'-UTR) of an mRNA, translation of a downstream coding sequence is directly controlled by TetR and tetracycline analogs. In endogenous and synthetic 5'-UTR contexts, this system efficiently regulates the expression of multiple target genes, and is sufficiently stringent to distinguish functional from non-functional RNA-TetR interactions. Using a reverse TetR variant, we illustrate the potential for expanding the regulatory properties of the system through protein engineering strategies.
PubMed ID: 22275521
MeSH Terms: 5' Untranslated Regions*; Animals; Aptamers, Nucleotide/chemistry*; Aptamers, Nucleotide/metabolism; Cell-Free System; Gene Expression Regulation*; Polyribosomes/metabolism; Protein Biosynthesis*; Rabbits; Repressor Proteins/metabolism*; Saccharomyces cerevisiae/genetics