RETRACTED ARTICLE: Discovery of iron-sensing bacterial riboswitches

Abstract

Despite the central role of iron in biology, our understanding of how cells sense iron is limited to protein-dependent mechanisms. Here, we report the discovery of iron-sensing riboswitches (named Sensei). Present across bacterial phyla, these RNAs reside in the 5′ untranslated regions or within coding regions of messenger RNAs (mRNAs) encoding iron-related proteins. These riboswitches bind the reduced form of iron with high specificity. Iron binding causes conformational changes in the riboswitch that alter the accessibility of conserved nucleotides, ultimately enabling a genetic response. Sensei–iron interactions result in increased translation of the riboswitch-associated mRNA in vivo, thus positioning these riboswitches as true metalloregulators. Learning from natural Sensei RNAs, we engineer metal selectivity, successfully converting a nickel/cobalt sensing riboswitch to exclusively bind iron and a Sensei RNA to now exclusively recognize cobalt. We thus define the sequence and structural space of iron-sensing RNAs and open avenues for the design of RNA-based biosensors. A family of riboswitches named Sensei that specifically sense iron has been discovered and characterized, which enables the authors to engineer metal ion sensing riboswitches to convert their metal selectivity.