A chemical probe based on the PreQ₁ metabolite enables transcriptome-wide mapping of binding sites.

ABSTRACT: The role of metabolite-responsive riboswitches in regulating gene expression in bacteria is well known and makes them useful systems for the study of RNA-small molecule interactions. Here, we study the PreQ₁ riboswitch system, assessing sixteen diverse PreQ₁-derived probes for their ability to selectively modify the class-I PreQ₁ riboswitch aptamer covalently. For the most active probe (11), a diazirine-based photocrosslinking analog of PreQ₁, X-ray crystallography and gel-based competition assays demonstrated the mode of binding of the ligand to the aptamer, and functional assays demonstrated that the probe retains activity against the full riboswitch. Transcriptome-wide mapping using Chem-CLIP revealed a highly selective interaction between the

SUBMITTER: Balaratnam S 

PROVIDER: S-EPMC8494917 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature