TitleDiscovery of iron-sensing bacterial riboswitches.
Publication TypeJournal Article
Year of Publication2020
AuthorsBandyopadhyay S, Chaudhury S, Mehta D, Ramesh A
JournalNat Chem Biol
Date Published2020 Oct 05
ISSN1552-4469
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.

DOI10.1038/s41589-020-00665-7
Alternate JournalNat Chem Biol
PubMed ID33020663
Grant ListIA/I/14/2/501521 / / DBT India Alliance (Wellcome Trust/DBT India Alliance) /
ECR/2016/001593 / / DST | Science and Engineering Research Board (SERB) /