Abstract：
:Riboswitches are naturally occurring RNA aptamers that regulate gene expression by binding to specific small molecules. Riboswitches control the expression of essential bacterial genes and are important models for RNA-small molecule recognition. Here, we report the discovery of a class of synthetic small molecules that bind to PreQ1 riboswitch aptamers. These molecules bind specifically and reversibly to the aptamers with high affinity and induce a conformational change. Furthermore, the ligands modulate riboswitch activity through transcriptional termination despite no obvious chemical similarity to the cognate ligand. X-ray crystallographic studies reveal that the ligands share a binding site with the cognate ligand but make different contacts. Finally, alteration of the chemical structure of the ligand causes changes in the mode of RNA binding and affects regulatory function. Thus, target- and structure-based approaches can be used to identify and understand the mechanism of synthetic ligands that bind to and regulate complex, folded RNAs.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Connelly CM,Numata T,Boer RE,Moon MH,Sinniah RS,Barchi JJ,Ferré-D'Amaré AR,Schneekloth JS Jrdoi
10.1038/s41467-019-09493-3subject
Has Abstractpub_date
2019-04-02 00:00:00pages
1501issue
1issn
2041-1723pii
10.1038/s41467-019-09493-3journal_volume
10pub_type
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