RNA quadruplex-based modulation of gene expression

RNA-based modules such as riboswitches represent straightforward and simplified approaches for the regulation of gene expression, as no additional proteins are needed. G-rich sequences are known to adopt stable four-stranded structures, and such quadruplexes have been suspected to play important roles in key functions such as the control of gene expression. Here we demonstrate that RNA quadruplexes readily form in vivo. We have constructed mRNA-based G-rich elements that mask the ribosome binding site by folding into four-stranded structures. The suppression of gene expression correlates with the stability of inserted G quadruplexes. Moreover, quadruplexes with moderate stability respond to changes in temperature, thus behaving as artificial RNA thermometers. In conclusion, we introduce tuneable mRNA-based devices that enable modulation of gene expression by a predictable but thus far unknown mechanism.