The Second Class of Tetrahydrofolate (THF-II) Riboswitches Recognizes the Tetrahydrofolic Acid Ligand via Local Conformation Changes

Riboswitches are regulatory noncoding RNAs found in bacteria, fungi and plants, that modulate gene expressions through structural changes in response to ligand binding. Understanding how ligands interact with riboswitches in solution can shed light on the molecular mechanisms of this ancient regulat...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-06, Vol.23 (11), p.5903
Main Authors: Zhang, Minmin, Liu, Guangfeng, Zhang, Yunlong, Chen, Ting, Feng, Shanshan, Cai, Rujie, Lu, Changrui
Format: Article
Language:English
Subjects:
3D modeling
Acylation
Amino acids
Binding
Biosynthesis
Carbon
Chromatography
Conformation
conformation switching
Drug development
Gene expression
Ligands
Metabolism
Metabolites
Molecular modelling
noncoding RNAs
riboswitch
Riboswitches
Tetrahydrofolic acid
THF-II riboswitch
Vitamin B
X-ray scattering
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Summary:Riboswitches are regulatory noncoding RNAs found in bacteria, fungi and plants, that modulate gene expressions through structural changes in response to ligand binding. Understanding how ligands interact with riboswitches in solution can shed light on the molecular mechanisms of this ancient regulators. Previous studies showed that riboswitches undergo global conformation changes in response to ligand binding to relay information. Here, we report conformation switching models of the recently discovered tetrahydrofolic acid-responsive second class of tetrahydrofolate (THF-II) riboswitches in response to ligand binding. Using a combination of selective 2'-hydroxyl acylation, analyzed by primer extension (SHAPE) assay, 3D modeling and small-angle X-ray scattering (SAXS), we found that the ligand specifically recognizes and reshapes the THF-II riboswitch loop regions, but does not affect the stability of the P3 helix. Our results show that the THF-II riboswitch undergoes only local conformation changes in response to ligand binding, rearranging the Loop1-P3-Loop2 region and rotating Loop1 from a ~120° angle to a ~75° angle. This distinct conformation changes suggest a unique regulatory mechanism of the THF-II riboswitch, previously unseen in other riboswitches. Our findings may contribute to the fields of RNA sensors and drug design.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23115903