Structural, Functional, and Taxonomic Diversity of Three PreQ1 Riboswitch Classes

Previously, two riboswitch classes have been identified that sense and respond to the hypermodified nucleobase called prequeuosine1 (preQ1). The enormous expansion of available genomic DNA sequence data creates new opportunities to identify additional representatives of the known riboswitch classes and to discover novel classes. We conducted bioinformatics searches on microbial genomic DNA data sets to discover numerous additional examples belonging to the two previously known riboswitch classes for preQ1 (classes preQ1-I and preQ1-II), including some structural variants that further restrict ligand specificity. Additionally, we discovered a third preQ1-binding riboswitch class (preQ1-III) that is structurally distinct from previously known classes. These findings demonstrate that numerous organisms monitor the concentrations of this modified nucleobase by exploiting one or more riboswitch classes for this widespread compound. [Display omitted] •Additional variant types of class I and II preQ1 riboswitches have been discovered•A third riboswitch class that senses preQ1 has been discovered and validated•Our findings expand the bacterial lineages that exploit preQ1-sensing riboswitches McCown et al. identify variants within two known riboswitch classes and a previously unknown riboswitch class that sense prequeuosine1, a nearly ubiquitous nucleobase with an unclear biological role. Phylogenetic analysis of these RNAs suggests they use distinct recognition strategies for this ancient compound.