Journal
NATURE CHEMICAL BIOLOGY
Volume 13, Issue 9, Pages 968-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2427
Keywords
-
Categories
Funding
- University of North Carolina at Chapel Hill
- NIH [R01 GM114432]
Ask authors/readers for more resources
Riboswitches control gene expression through ligand-dependent structural rearrangements of the sensing aptamer domain. However, we found that the Bacillus cereus fluoride riboswitch aptamer adopts identical tertiary structures in solution with and without ligand. Using chemical-exchange saturation transfer (CEST) NMR spectroscopy, we revealed that the structured ligand-free aptamer transiently accesses a low-populated (similar to 1%) and short-lived (similar to 3 ms) excited conformational state that unravels a conserved 'linchpin' base pair to signal transcription termination. Upon fluoride binding, this highly localized, fleeting process is allosterically suppressed, which activates transcription. We demonstrated that this mechanism confers effective fluoride-dependent gene activation over a wide range of transcription rates, which is essential for robust toxicity responses across diverse cellular conditions. These results unveil a novel switching mechanism that employs ligand-dependent suppression of an aptamer excited state to coordinate regulatory conformational transitions rather than adopting distinct aptamer ground-state tertiary architectures, exemplifying a new mode of ligand-dependent RNA regulation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available