Bacterial Riboswitches Cooperatively Bind Ni2+ or Co2+ Ions and Control Expression of Heavy Metal Transporters

• Published in: Molecular cell 2015-03, Vol.57 (6), p.1088-1098
• Main Authors: Furukawa, Kazuhiro, Ramesh, Arati, Zhou, Zhiyuan, Weinberg, Zasha, Vallery, Tenaya, Winkler, Wade C., Breaker, Ronald R.
• Format: Article
• Language: English
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2015.02.009

Bacteria regularly encounter widely varying metal concentrations in their surrounding environment. As metals become depleted or, conversely, accrue to toxicity, microbes will activate cellular responses that act to maintain metal homeostasis. A suite of metal-sensing regulatory (“metalloregulatory”) proteins orchestrate these responses by allosterically coupling the selective binding of target metals to the activity of DNA-binding domains. However, we report here the discovery, validation, and structural details of a widespread class of riboswitch RNAs, whose members selectively and tightly bind the low-abundance transition metals, Ni2+ and Co2+. These riboswitches bind metal cooperatively, and with affinities in the low micromolar range. The structure of a Co2+-bound RNA reveals a network of molecular contacts that explains how it achieves cooperative binding between adjacent sites. These findings reveal that bacteria have evolved to utilize highly selective metalloregulatory riboswitches, in addition to metalloregulatory proteins, for detecting and responding to toxic levels of heavy metals. [Display omitted] •NiCo RNA is the first conserved riboswitch class that responds to transition metals•NiCo selectively recognizes cobalt or nickel, binding with positive cooperativity•NiCo riboswitches control metal homeostasis by regulating metal transport proteins Metal ions serve many essential roles but are toxic in excess; therefore, organisms utilize proteins that allosterically couple metal-sensing sites to control of gene expression. Furukowa et al. discover that certain noncoding RNAs can also perform this task, suggesting that such metalloregulation is not limited to proteins.